Infections in Immunocompromised Rheum PT

Crit Care Clin 18 (2002) 931 956
Infections in the immunocompromised rheumatologic patient

Stephen B. Greenberg, MD*
Departments of Medicine, Molecular Virology, and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA Ben Taub General Hospital, Houston, TX 77030, USA
Infections in immunocompromised patients with rheumatic diseases cause significant morbidity and mortality [1 51]. Because the clinical manifestations of infections are often indistinguishable from the underlying disease, recognition and treatment of these infections may be delayed [52 55]. The typical signs and symptoms of infection may be absent because of concomitant immunosuppressive therapies [56 61]. Potential pathogens include bacteria and less frequently encountered opportunistic agents [62 75]. For these reasons, infections are often difficult to diagnose and treat. Patients with systemic lupus erythematosus (SLE) are prone to infection of the CNS, lungs, urinary tract, skin, and soft tissue [76 79]. During the course of the disease, approximately 50% will have at least one infection. Infections in SLE patients are related to immunologic defects caused by the disease itself or by the therapy employed [5]. In addition, infections may be promoted by progression of the disease or by medical procedures such as arthrocentesis [80]. In SLE patients, infection is a cause of hospital admission as well as a leading complication following admission. In several series, infection is reported as the leading cause of death in SLE patients [4,20,24,30,48,50,51]. In patients with rheumatoid arthritis (RA), diminished survival is associated with comorbidities of the disease [54,81]. Major comorbidities include cardiovascular disease, malignancy, gastrointestinal disease, osteoporosis, and infection [5,8,11,19,27,29,82,83]. The infections are related to the immunosuppressive therapy as well as to the intrinsic effects of RA on certain organ systems, specifically the musculoskeletal system [38,39,55,60,84,85].
* Department of Medicine, Baylor College of Medicine. E-mail address: stepheng@bcm.tmc.edu (S.B. Greenberg). 0749-0704/02/$ see front matter D 2002, Elsevier Science (USA). All rights reserved. PII: S 0 7 4 9 - 0 7 0 4 ( 0 2 ) 0 0 0 2 2 - 2
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S.B. Greenberg / Crit Care Clin 18 (2002) 931956
Predisposing factors to infection The major predisposing factors to infection in patients with SLE or RA are known to overlap (Tables 1, 2). In SLE patients, alterations in phagocytic cells are common with disease activity [86]. Cellular immunity is impaired, as reflected by lymphopenia, decreased CD4 cell counts, and reduced cytokine production [87,88]. Reduced immunoglobulin and complement levels have also been reported in SLE patients [89]. Functional asplenia may reduce the elimination of bacteria from the blood stream [90,91]. The use of corticosteroids and immunosuppressive drugs is also a major risk factor for infection. Chronic inflammation in RA leads to bone and joint deformity that predisposes patients to local infections especially septic arthritis [3,11]. Recent analysis of infections in RA patients demonstrated the importance of duration of steroid use, the cumulative methotrexate dose, and the mean daily dose of D-penicillamine [19].
Immunologic effects of corticosteroid use Certain infectious diseases are associated with chronic steroid use [58]. Predisposition to these infections is attributed to the deleterious effects of steroids on the immune system [92,93]. Corticosteroid use will result in skin atrophy, easy bruising, and delayed wound healing. These conditions can result in increased access of skin flora to subcutaneous tissue and subsequent infection. Corticosteroid use also leads to neutrophilia, decreased migration of neutrophils to sites of inflammation, inhibition of chemotaxis, and decreased phagocytosis and intracellular killing of microorganisms. The effects of chronic steroid use on lymphocytes include lymphocytopenia and suppression of normal delayed hypersensitivity reactions [94]. Monocytic and macrophage activities can also be adversely affected by chronic steroid use. Serum IgG concentration is decreased after 3 to 5 days of corticosteroid use [95]. Although the total white blood cell (WBC) count may exceed 20,000/mm3 because of the increased release of mature neutrophils from the bone marrow and decreased exit of neutrophils from the circulation, the band and metamyelocyte percentage rarely exceeds 6% of the total count [60].
Table 1 Predisposing factors to infection in patients with SLE Alteration in phagocytic function Defects in cellular immunity Decreased production of immunoglobulin Low complement levels Reticulo-endothelial system impaired organism elimination Chronic use of corticosteroids and/or immunosuppressants
S.B. Greenberg / Crit Care Clin 18 (2002) 931956 Table 2 Predisposing factors to infection in patients with RA Chronic inflammation producing deformed bones and joints Chronic use of steroid and/or immunosuppressants
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Infections in corticosteroid-treated patients are those associated with defective phagocytic function and with some diminished cell-mediated immunity (Table 3) [96 98]. The incidence of infectious complications rises with increasing daily doses given for more than 4 weeks [44]. The relative risk ratio for infection was reported to be 1.6 in all patients receiving corticosteroids compared with those not receiving corticosteroids. Alternate-day steroid use reduces the risk of infection considerably. Lower doses of pulse methyl prednisolone to treat SLE flares also decrease the risk of serious infection [99].
Other immunosuppressive therapies Cytotoxic drugs affect the production of phagocytes and lymphocytes. Drugs such as cyclophosphamide, azathioprine, or methotrexate are often given in conjunction with corticosteroids in rheumatic diseases [100,101]. When cytotoxic drugs are given alone or with alternate-day steroids, there is a significant lowering of infectious complications. Cyclophosphamide causes neutropenia resulting from decreased production and increased destruction of neurtophils [102]. Hoffman et al reported on 158 patients with Wegeners granulomatosis who received cyclophosphamide and prednisone therapy [20]. Serious infections occurred in 46% of patients. Pneumonia caused by Staphylococcus aureus, Pseudomonas aeuginosa, and Haemophilus influenzae was the most frequent serious infection. Fungi were also identified. Half of the serious infections were observed in patients receiving daily prednisone therapy. Sixteen percent of infections were observed when cyclophosphamide was given alone. Bradley et al observed serious infections in a small group of patients with systemic vasculitis treated with cyclophosphamide [103]. More than half the patients had infections detected during 200 patient-months of follow up. The rate of infections in SLE patients with nephritis treated with cyclophosphamide plus low-dose steroids is the same as that seen in patients treated with high-dose steroids alone. Pulse cyclophosphamide therapy for lupus nephritis is associated with rates of infections similar to those of daily cytotoxic treatment [104]. Azathioprine and its metabolite inhibit protein synthesis. Treatment results in lymphopenia and suppressed immunoglobulin synthesis [60]. Neutrophil function seems to remain intact with azathioprine therapy. Neutropenia may result from bone marrow suppression, however. This neutropenia seems to be dose dependent. In a large study comparing cytotoxic medications in rheumatoid arthritis patients, the rate of infection was lower with azathioprine than with cyclophosphamide or methotrexate. Opportunistic infections are rarely reported
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Table 3 Predominant immunologic defects and pathogens associated with selected pharmacologic agents used in the treatment of rheumatic diseases Abnormality Qualitative defect of phagocytic function or neutropenia Agent Corticosteroids Cyclophosphamide and other alkylating agents Azathioprine Bacterial Gram-positive Staphylococcus aureus Streptococcal spp Nocardia spp Gram-negative Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa Other Enterobacteriaceae Mycobacterium spp Listeria monocytogenes Salmonella spp Nocardia spp Fungal Candidia spp Aspergillus spp Protozoal Viral S.B. Greenberg / Crit Care Clin 18 (2002) 931956
Defective cell-mediated immunity
Defective humoral immunity
Corticosteroids Cyclophosphamide Other alkylating agents Azathioprine Methotrexate Cyclosporin A Cyclophosphamide Corticosteroids (high-dose) Azathioprine
Histoplasma capsulatum Coccidioides immitis Cryptococcus neoformans
Pneumocystic carinii Toxoplasma gondii Strongyloides stercoralis
Cytomegalovirus Epstein-Barr virus Varicella-Zoster virus
Streptococcus pneumoniae Haemophilus influenzae
From Segal BH, Sneller MC. Infectious complications of immunosuppressive therapy in patients, with rheumatic diseases. Rheum Dis Clin North Am 1997;23:219 37; with permission.
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in patients receiving azathioprine alone. When azathioprine is used in combination with steroids, opportunistic infections are recorded. Methotrexate is immunosuppressive in high doses but is less so in the dosages used in treating rheumatoid arthritis [105]. Low-dose methotrexate can inhibit immunoglobulin synthesis and neutrophil chemotaxis and can cause bone marrow suppression [106,107]. Antibiotics with antiproliferative properties (ie, trimethoprim-sulfamethoxazole) should be used with caution in patients receiving methotrexate therapy. The infection rate in methotrexate-treated rheumatoid or psoriatric arthritis patients ranges from 0 to 20% per year [108 110]. Pneumocystis carinii pneumonia and herpes zoster are the most commonly reported opportunistic infections [111,112]. Less commonly identified opportunistic pathogens include Nocardia, Cryptococcus, Histoplasma, Aspergilla, Mycobacterium tuberculosis, and Listeria [107,113 120]. Although uncommon, low-dose weekly methotrexate is associated with opportunistic infections as early as a few weeks to several years after starting therapy [121,122]. When methotrexate was given with corticosteroids in Wegeners granulomatosis, Pneumocystis carinii pneumonia was reported in several patients [101]. Cyclosporin A binds to cyclophilin, an endogenous intracellular protein, resulting in a complex that inhibits the activity of calcineuin. Calcineuin is required for transmitting activity signals from the T-cell receptor [123]. Infections with cyclosporin therapy relate to those associated with defective cellmediated immunity. Lymphocytotoxic monoclonal Ab, CAMPATH-IH, is a humanized monoclonal antibody that recognizes the antigen CD52 that is expressed on B, T, and natural killer (NK) cells and macrophages. The beneficial effects of this therapy in rheumatoid arthritis patients have been transient. Although NK cells, B cells, and monocytes returned to normal levels within 3 to 6 months, CD4+ and CD8+ T cells remained low for years [22]. Among 13 deaths in patients previously receiving CAMPATH-IH for RA, 4 had pneumonias as the underlying cause of death. Among 18 patients with major infections after CAMPATH-IH therapy, septicemia and pneumonia were the most frequent types of infections. Minor infections following CAMPATH-IH therapy included herpes simplex, varicella-zoster virus infections, and bronchitis. The authors conclude that there was no unusual increase in number or types of infections in these RA patients treated with CAMPATH-IH.
New therapies for rheumatoid arthritis (infliximab and etanercept) Two new biologic agents used in the treatment of rheumatoid arthritis target tumor necrosis factor-a (TNF-a). A chimeric IgG1 monoclonal antibody with high affinity for human TNF-a, infliximab has been shown to improve joint pain and swelling in RA patients [124 129]. Recent reports, however, have shown an increase in cases of tuberculosis, listeria, and histoplasmosis (Table 4) [130 132]. Etanercept is a recombinant human TNF receptor protein that binds TNF-a. Because of the drugs half-life, it can be administered subcutaneously
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Table 4 Reported infections with treatment of RA with biologic response modifiers infliximab and etanercept Infection Mycobacterium tuberculosis Histoplasmosis Pneumocystis carinii Coccidioidomycosis Cryptococcosis Infliximab treatment 92 9 12 2 2 Etanercept treatment 11 1 5 0 3
Adapted from US Food and Drug Administration. 2001. Available at: http://vapbm.org/criteria/ lef_etan_infcriteria.pdf. Accessed October 1, 2001; with permission.
two times per week. It has been reported to be associated with tuberculosis infections [133], although a recent study has suggested that tuberculosis in RA patients increased before these new therapies became available [134].
Clinical presentations in systemic lupus erythematosus Fever in SLE patients is commonly observed with disease activity [135,136]. Eighty percent of patients will have fever documented at least once during this illness. In one series, only 23% of febrile episodes were caused by infections [137]. Clinically it was difficult to distinguish infection from active SLE. Shaking chills occurred in significantly more patients with proven infections (68% versus 27%). Neutrophilic leukocytosis was detected more frequently in febrile patients with infection. In all patients with rheumatic diseases, fever should prompt an immediate evaluation. Besides a complete history and physical examination, a chest roentgenogram, blood and other appropriate cultures, and assessment of the underlying disease activity are all appropriate. Skin lesions in a febrile patient with rheumatic disease should be examined carefully and biopsied for culture and pathologic review. If signs and symptoms of pneumonia are present, careful review of laboratory and clinical findings should help distinguish infection from active rheumatic disease or a drug reaction [138,139]. Bacteria are the most common cause of pneumonia and reflect the agents in the community. The most frequently detected opportunistic pathogen in rheumatic diseases is Pneumocystic carinii pneumonia, although fungi, mycobacteria, Nocardia, and cytomegalovirus have also been reported [17,20,67,103,140 142]. Onset of symptoms over a few days points to a bacterial cause. A progressive course over days to weeks is more suggestive of an opportunistic pathogen or active rheumatic disease flare. Exposure to individuals with tuberculosis should be sought. History of travel to other countries or regions of the United States should be obtained [143]. Exposure to young children with acute respiratory viral illness should also be reviewed. On roentgenogram studies, pulmonary infiltrates may have varying patterns that suggest either an infectious or noninfectious diagnosis (Table 5) [144 148]. If the patient is producing sputum, a Grams stain and culture should be sent to
S.B. Greenberg / Crit Care Clin 18 (2002) 931956 Table 5 Differential diagnosis of pulmonary infiltrates in patients with rheumatic diseases Radiographic pattern Localized infiltrates Infectious causes Bacterial pneumonia (including Legionella spp) Mycobacteria spp Opportunistic fungi Aspergillus spp Histoplasma capsulatum Coccidioides immitis Cryptococcus neoformans (uncommon) Pneumocystis carinii Bacterial pneumonia (hematogenous spread) Mycoplasma pneumoniae Chlamydia spp Mycobacteria spp (miliary pattern) Opportunistic fungi Viral Influenza virus Cytomegalovirus Varicella-Zoster virus (rare) Septic emboli Staphylococcus aureus Pseudomonas aeruginosa Mycobacteria spp Nocardia spp Opportunistic fungi Noninfectious causes Wegeners granulomatosis Churg-Strauss syndrome Pulmonary embolus
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Diffuse infiltrates
Nodules or nodular infiltrates
Systemic lupus erythematosus Rheumatoid arthritis Microscopic polyangiitis Wegeners granulomatosis Churg-Strauss syndrome Scleroderma Sjogrens syndrome Dermatomyositis/polymyositis Pulmonary edema Drug-induced Methotrexate Cyclophosphamide (rare) Azathioprine (rare) Wegeners granulomatosis Churg-Strauss syndrome Rheumatoid arthritis Lymphoma
Adapted from Segal BH, Sneller MC. Infectious complications of immunosuppressive therapy in patients with rheumatic diseases. Rheum Dis Clin North Am 1997;23:219 37; with permission.
the laboratory. Thoracentesis should be performed if pleural fluid is detected. Depending on the severity of the illness and the extent of the pulmonary infiltrates, a more expedient approach may require bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy. The isolation of Candida from respiratory secretions does not usually indicate infection but rather colonization. Aspergillus spp recovered from respiratory secretions may reflect either colonization or invasive disease. Only the detection of Aspergillus or Candida from tissue samples is the standard for diagnosing these opportunistic fungal infections [149]. Cytomegalovirus recovered from BAL should also be interpreted with caution when quantitative cultures or tissue biopsy specimens yield evidence of invasive viral infection [150]. Open-lung biopsy should be reserved for patients with unresponsive localized lesions or cavities. Central nervous system infections in patients with rheumatic diseases may be difficult to differentiate from the clinical manifestations produced by the diseases
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themselves [151,152]. Although CNS infections have been reported in Wegeners granulomatosis, polyarteritis nodosa and Behcets disease, they are most difficult to diagnose in SLE because of the high frequency of neuropsychiatric symptoms [153]. Wong et al reported that 50% of episodes of neuropsychiatric disease in SLE patients were caused by a CNS or systemic infection [154]. Although other series reported a lower incidence of CNS infections, they agree with the difficulty in clinically distinguishing infections from CNS lupus [155,156]. These patients may not have the typical signs and symptoms of meningitis. Therefore, patients with unexplained headache, personality changes, confusion, and focal neurologic findings should have immediate computed tomographic (CT) scan or MR imaging and lumbar puncture. Serum markers of infection in systemic lupus erythematosus C-reactive protein (CRP) is an acute-phase protein of the innate host defense against bacterial pathogens. Elevated CRP levels in serum of SLE patients have been studied as a marker of disease activity versus the presence of coexistent infection. In a recent retrospective case control study in Korean patients with SLE, Suh et al report that CRP levels greater than 50 mg/L are suggestive of infection [157]. Similar findings were reported in earlier studies [158 160]. C-reactive protein levels during SLE flares can range from 1 to 375 mg/L with a median level of 16.5 mg/L [161]. Systemic lupus erythematosis flares associated with serositis had higher median levels (76 mg/L) than seen in flares without serositis (16 mg/L) [161]. Local infections had CRP levels between 10 mg/L and 50 mg/L. Fever may be observed in infected SLE patients even with nonelevated CRP levels [162]. In a recent study, elevated interleukin (IL)-1 receptor antagonist levels, but not IL-6, IL-1b or TNF-a levels, were markers for elevated CRP levels in untreated SLE patients [163]. Elevated serum ferritin levels have been reported to be another marker of SLE disease activity in untreated patients [164]. It is unclear whether ferritin levels can be used to distinguish infection from disease activity. Fibrinogen level, another acute phase reactant, was found to increase with age regardless of SLE disease activity [165]. Procalcitonin (PCT) levels in the serum have been reported to increase in bacterial or fungal infections but not in viral infections. A recent prospective study in 19 patients with SLE and fever reported elevated PCT levels in nonviral infection in 9 SLE patients but not in 3 viral-infected SLE patients and not in 7 patients with an SLE flare [166]. The elevated PCT levels returned to normal during defervescence. Procalcitonin and CRP levels may prove useful when used together in febrile SLE patients.
Mortality from infections in systemic lupus erythematosus One of the most common causes of death in SLE patients is infection [46,167,168]. Three recent cohort studies have documented the importance of
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infections as a cause of death in these patients, and many other studies over 3 decades from many different countries have reported infectious death rates of 0 to 67%, with a mean of 24% [4,30,148]. Six studies following patients from the onset of diagnosis (cohort studies) have reported infectious death rates from 6% to 67%, with a mean rate of 24.5% [4,24,30,32,40,41,43,46,48,167,169,170]. Infectious causes of death may be underreported, because autopsy studies have found several opportunistic infections that had not been diagnosed before death [36,67]. Serious infections in systemic lupus erythematosus Serious infections in SLE patients often involve theCNS, blood, lungs, or urinary tract [171 174]. The commonly isolated organisms that cause meningitis in non SLE patients also infect SLE patients. Other opportunistic organisms, such as Legionella, Nocardia, Cryptococcus, Mycobacteria, Toxoplasmosis, and Listeria, are also important causes in corticosteroid-treated SLE patients [175 180]. The presentation and etiology of bacteremia or fungemia in SLE patients is similar to that in other patients [181]. Disseminated neisserial and nontyphoid Salmonella infections, however, seem to be more common in SLE patients [182 184]. Community-acquired pneumonia occurs with the same pathogens in SLE patients as in the general population. Systemic lupus erythematosis patients treated with corticosteroids or immunosuppressive medications may have pneumonia caused by Legionella, Pneumocystis carinii, Nocardia, Mycobacterium tuberculosis, or Cryptococcus neoformans [185 190]. Urinary tract infections caused by gram-negative bacteria are common in SLE patients and may be accompanied by septicemia [5]. Candida albicans is a common cause of urinary tract infections in corticosteroid-treated SLE patients. Skin infections such as cellulitis are caused by Staphylococcus aureus and group A streptococci. Herpes zoster frequently affects steroid-treated SLE patients. Cases of secondary syphilis have been reported to mimic SLE [191]. Risk factors for serious bacterial infections include cytotoxic medications, corticosteroids, proteinuria, renal insufficiency, and active SLE [192,193]. Up to 37% of patients treated with cyclophosphamide develop a serious infection [192]. To most clinicians, the ability to differentiate an SLE flare from infection is a significant challenge. Because there is overlap between the organ involvement by SLE with that seen with infectious organisms, early recognition and appropriate treatment may be difficult [194,195]. Lupus cerebritis has many of the clinical findings seen in bacterial meningitis [196,197]. A stiff neck is far less common in lupus cerebritis than in bacterial meningitis [153]. Findings in the cerebrospinal fluid with bacterial meningitis include neutrophilic pleocytosis, low cerebrospinal fluid (CSF) glucose, and increased lactic acid levels. Findings are similar in lupus cerebritis, except the lactic acid levels are normal. A decreased C4 level in the CSF is helpful in the diagnosis of SLE cerebritis [153]. Although earlier publications have suggested that there are typical changes on CT and MR imaging scans of the brain in lupus
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cerebritis, more recent series have suggested the observed abnormalities were nonspecific [198]. Bacteria are the cause of most infections in SLE patients [36,67,169,170, 199,200]. Escherichia coli is a common pathogen, but Staphylococcus aureus and Streptococcus pneumoniae have also been isolated [201]. Streptococcus pneumoniae may cause epiglottitis, pneumonia, sepsis, or soft tissue infections [202 204]. Nocardia infections of the lung and CNS have been reported but are infrequent. Salmonella infections Salmonella are aerobic gram-negative bacilli that can cause serious infections in SLE patients [182,205 208]. Salmonella are grouped by the carbohydrate side chain on the cell wall. Salmonella typhosa belong to group D Salmonella. Nontyphoid salmonella bacteremias, especially group B and D, have been reported in SLE patients [184,209]. Most cases occur during periods of active SLE and may be the presenting illness of SLE. Most of these patients have been treated with corticosteroids or other immunosuppressive drugs. Systemic lupus erythematosus patients may be prone to Salmonella infections because of inadequate opsonization, impaired mononuclear phagocytosis, hyposplenism, or low serum complement levels. Although fever at presentation is the rule, 15% to 20% of patients may be afebrile. Clinical syndromes include gastroenteritis, arthritis, and pneumonia [210,211]. Other less common diagnoses included cellulitis, osteomyelitis, urinary tract infection, or meningitis [212 214]. Most patients are not toxic or septic on admission. Laboratory findings include anemia, lymphopenia, and hypoalbuminerima. Elevated CRP levels ( > 10 mg/L) are commonly reported. Anti-dsDNA is raised in more than 85% of patients. Recurrences following treatment have been seen. With Salmonella bacteremia, a 2-week course of appropriate antibiotic is indicated [215]. Salmonella gastroenteritis without bacteremia should not be treated with antibiotics, because antibiotics have been shown to cause prolonged fecal carriage and increased relapse [216]. Death is uncommon but can occur. If recurrence or persistent bacteremia is observed, a careful search for carriage in the gallbladder or detection of a mycotic aneurysm, arthritis, or osteomyelitis should be undertaken. Neisseria infections Neisserial infections have been reported in SLE and may present clinically as a lupus flare [183]. These patients are often young women with renal disease and low C3 and C4 levels. Complement deficiencies may be acquired or congenital. Arthritis is a common presentation of disseminated neisserial infection [217]. Meningitis and, less commonly, endocarditis have been reported [218 220]. Although there are few data on the usefulness of immune response to meningococcal vaccine in SLE patients, many authorities recommend vaccination of these SLE patients [221].
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Mycobacterial infections Mycobacteria tuberculosis has been found in SLE patients, especially in geographic areas with a high rate of purified protein derivative (PPD) positivity [42,222 225]. Extrapulmonary disease is common [226 228]. Most of the patients were receiving corticosteroid or immunosuppressive therapy [229,230]. A negative PPD in patients receiving corticosteroids cannot be used to rule out tuberculosis. Cases of nontuberculosis mycobacterial infections in SLE patients have been reported [231 235]. Fungal infections The fungi reported to cause infection in SLE patients are Candida, Aspergillus, Cryptococcus, and Pneumocystis carinii [236 239]. Other fungi have been rarely reported [76,240 247]. In the series by Hellman et al, Candida spp was the opportunistic infection leading to death in 6 of 24 patients [67]. Systemic lupus erythematosis patients receiving immunosuppressive drugs or antibiotics in the hospital should be considered candidates for these fungal infections. Pneumocystis carinii pneumonia (PCP) is an uncommon but potentially fatal infection in SLE patients [248 254] and in other patients with connective tissue diseases [255 257]. One study reported on the frequency of PCP in Wegeners granulomatosis patients who were lymphopenic and immunosuppressed [258]. Lymphopenia was also found in SLE patients who developed PCP [250]. A diagnosis of interstitial pulmonary fibrosis was made by characteristic chest rroentgenogram or CT scan findings and was reported in all the SLE patients who developed PCP, but it is unclear from the report when interstitial pulmonary fibrosis was found in relation to clinical PCP. Of seven patients with PCP in this series, three died. Viral infections Most viral infections in SLE patients have not been proved to be more frequent or more severe than in non SLE patients [259,260]. Herpes zoster has been reported to occur more frequently, but not with more disseminated disease, than in other immunosuppressed patients [67,261 263]. Cytomegalovirus viruria was not shown to be associated with serologic activity in SLE patients followed longitudinally [264,265] but may be associated with SLE flares [266]. Other herpesviruses have not been found to cause SLE complications or to lead to increased disease activity [5,267 271]. Human immunodeficiency virus infection has been reported to be associated with improvement in SLE patients and with the loss of autoantibodies [272]. Progressive multifocal leukoencephalopathy has also been reported in SLE patients [273]. Human parvovirus B19 infection is associated with fever, anemia, thrombocytopenia, and leukopenia [274]. Antinuclear antibodies may also be detected following this infection [275]. Therefore, active SLE or juvenile rheumatoid
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arthritis must be in the differential diagnosis when considering active parvovirus B19 infection [276,277]. In addition, occasional SLE patients with human parvovirus B19 infection have had flares reported during the acute infection [278 280].
Infections in rheumatoid arthritis Early studies with RA patients suggested that infections account for approximately 25% of all deaths [29,59,85,105]. As with SLE, it has been difficult to separate the effects of immunosuppressive drugs used in treatment from the disease itself. Low-dose methotrexate treatment in RA patients seems to increase infection rates [5,108]. Postoperative infections in RA patients have also been related to methotrexate use [121]. Stuck et al found no increased risk of infection among patients taking prednisone at a daily dose of less than 10 mg or a cumulative dose of less than 700 mg [61]. Two retrospective case-control studies of infections in RA patients found no increased rate in common infections compared with patients with osteoarthritis [281,282]. These studies were of short duration and were based on self-reported hospitalized patients [11]. A recent population-based study was reported in abstract form from an incidence cohort in Rochester, Minnesota, between 1955 and 1994 [81]. Rheumatoid arthritis patients were followed from first diagnosis along with an age- and sex-matched control group for a mean of 12.7 and 15 years, respectively (Table 6). The total case incidence per 100 person-years for all infections was 19.23 versus 12.65 for RA patients and the control group, respectively (rate ratio = 1.52). Septic arthritis and osteomyelitis had rate ratios of 14.87 and 10.62, respectively. The rates of skin and soft tissue infections were approximately three times higher in RA patients than in controls. Septicemia, pneumonia, lower
Table 6 Incidence cohort of RA patients followed from 1955 1994 at the Mayo Clinic Infection Septicemia Septic arthritis Osteomyelitis Pneumonia Lower respiratory tract infection Urinary tract infection Skin or soft tissue Intra-abdominal Other Rate ratio 1.5 14.9 10.6 1.6 1.9 1.1 3.3 2.8 2.0
609 rheumatoid arthritis cases followed 12.7 years (mean); 609 controls followed 15 years (mean). Data from Doran MF, Pond GR, Crowson CS, et al. Risk of infection in persons with rheumatoid arthritis compared to controls: a population-based study [abstract]. Arthritis Rheum 2001;44:S105.
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respiratory tract, and intra-abdominal infections were also more frequent in RA patients than in the control group. Septic arthritis is a major infection in RA patients [80,283 287]. Nolla et al reported on recent cases of septic arthritis in RA patients seen between 1990 and 1998 [286]. All patients had long-standing disease and were being treated with corticosteroids. Isolated bacteria included Staphylococcus aureus, gram-negative bacilli, anaerobes, and Streptococcus pneumoniae. The principal source of infection is thought to be the skin. There was often a delay in diagnosis of a few days to several weeks. Half of the patients had fever. Two patients died. Of those who lived, most had worsening of their joint function. Older series have commented on the importance of Staphylococcus aureus in septic arthritis [288 290]. Less common organisms have been recovered in individual cases [291 298]. Recent studies have pointed to the emergence of Streptococcus pneumoniae as a cause of septic arthritis in these patients [299 301]. Most cases of septic arthritis are monoarticular, but 10% to 20% may be polyarticular [80,288]. The joints most frequently infected are the knee, elbow, and wrist. Patients with poor outcomes often have delayed diagnosis [302]. All acutely inflamed joints in RA patients should be aspirated for cell count, Grams stain, and culture of the synovial fluid. Repeated needle aspiration or surgical drainage should be considered in addition to prompt antibiotic therapy. Respiratory infections, especially pneumonia, have been reported with RA [303,304]. In addition to the usual community-acquired agents, opportunistic pathogens such as atypical mycobacteria and Pneumocystis carinii can be found [305 309]. As in SLE, these opportunistic pathogens may be related to immunosuppressive therapy and not to RA per se [96]. Recent experience with infliximab and etanercept has highlighted the risk of tuberculosis and fungal infections in RA patients treated with these agents [126,127].
Vaccination for systemic lupus erythematosus and rheumatoid arthritis patients Because of the morbidity associated with pneumococcal and influenza virus infection, it has been recommended that SLE and RA patients receive approved inactivated vaccines [310,311]. The two major issues in vaccine administration of these patients are (1) the expected immune response following vaccination, and (2) the potential for worsening the underlying disease. Recent studies have failed to find a relationship between the administration of the pneumococcal vaccine and the influenza virus vaccine and SLE or RA flares or decrease in clinical function by these patients. Some studies, however, have suggested that these patients may hae a less-than-optimal immune response to these vaccines. Meningococcal vaccines should probably be given to SLE patients. The longterm safety of hepatitis B vaccine or live attenuated viral vaccines has not been studied systematically in controlled trials.
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Summary Immunocompromised patients with rheumatic diseases have an increased risk of infections. A major risk factor for infection seems to be the immunosuppressive therapy used. Newer therapies for RA may lead to increased rates of infection by opportunistic pathogens such as Mycobacteria tuberculosis. Because disease manifestation may mimic signs and symptoms of infection, prompt diagnosis may be difficult. Familiarity with the likely infections and their causes should aid in obtaining the appropriate culture specimens.
References
[1] Al-Mayouf SM, Al-Jumaah S, Bahabri S, et al. Infections associated with juvenile systemic lupus erythematosus. Clin Exp Rheumatol 2001;19:748 50. [2] Ansell SM, Bedhesi S, Ruff B, et al. Study of critically ill patients with systemic lupus erythematosus. Crit Care Med 1996;24:981 4. [3] Baum J. Infection in rheumatoid arthritis. Arthritis Rheum 1971;14:135 7. [4] Bellomio V, Spindler A, Lucero E, et al. Systemic lupus erythematosus: mortality and survival in Argentina. A multicenter study. Lupus 2000;9:377 81. [5] Bouza E, Moya JG, Munoz P. Infections in systemic lupus erythematosus and rheumatoid arthritis. Infect Dis Clin North Am 2001;15:335 61 [vii.]. [6] Bujan S, Labrador M, Balada E, et al. Trends in mortality in a cohort of lupus patients [abstract]. Lupus 2001;10:S76. [7] Calabrese LH. Vasculitis of the central nervous system. Rheum Dis Clin North Am 1995;21: 1059 76. [8] Corley DE, Winterbauer RH. Collagen vascular diseases. Semin Respir Infect 1995;10:78 85. [9] Cunha B. Infections in SLE. Infect Dis Clin Pract 1997;21:41 2. [10] Cunha BA. Infections in nonleukopenic compromised hosts (diabetes mellitus, SLE, steroids, and asplenia) in critical care. Crit Care Clin 1998;14:263 82. [11] Doran MF, Gabriel SE. Infections in rheumatoid arthritis a new phenomenon? J Rheumatol 2001;28:1942 3. [12] Dubois EL, Tuffanelli DL. Clinical manifestations of systemic lupus erythematosus. Computer analysis of 520 cases. JAMA 1964;190:104 11. [13] Duffy KN, Duffy CM, Gladman DD. Infection and disease activity in systemic lupus erythematosus: a review of hospitalized patients. J Rheumatol 1991;18:1180 4. [14] Fauci AS, Haynes BF, Katz P, et al. Wegeners granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 1983;98:76 85. [15] Font J, Cervera R, Pallares L, et al. Infection in systemic lupus erythematosus (SLE): a controlled and prospective study [abstract]. Arthritis Rheum 1990;33:S130. [16] Formiga Perez F, Moga Sampere I, Canet Gonzalez R, et al. Infection and systemic lupus erythematosus: analysis of a series of 145 patients. Rev Clin Esp 1993;193:105 9. [17] Ginzler E, Diamond H, Kaplan D, et al. Computer analysis of factors influencing frequency of infection in systemic lupus erythematosus. Arthritis Rheum 1978;21:37 44. [18] Godeau B, Mortier E, Roy PM, et al. Short and longterm outcomes for patients with systemic rheumatic diseases admitted to intensive care units: a prognostic study of 181 patients. J Rheumatol 1997;24:1317 23. [19] Hernandez-Cruz B, Cardiel MH, Villa AR, et al. Development, recurrence, and severity of infections in Mexican patients with rheumatoid arthritis. A nested case-control study. J Rheumatol 1998;25:1900 7. [20] Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 1992;116:488 98.
945
[21] Inman RD. The role of infection in chronic arthritis. J Rheumatol Suppl 1992;33:98 104. [22] Issacs JD, Greer S, Sharma S, et al. Morbidity and mortality in rheumatoid arthritis patients with prolonged and profound therapy-induced lymphopenia. Arthritis Rheum 2001;44: 1998 2008. [23] Janwityanuchit S, Totemchokchyakarn K, Krachangwongchai K, et al. Infection in systemic lupus erythematosus. J Med Assoc Thai 1993;76:542 8. [24] Jonsson H, Nived O, Sturfelt G. Outcome in systemic lupus erythematosus: a prospective study of patients from a defined population. Medicine (Baltimore) 1989;68:141 50. [25] Juega J, Pedreira JD, Adega M, et al. Infection in systemic lupus erythematosus. Rev Clin Esp 1989;184:245 6. [26] Klein NC, Cunha BA. Infections in systemic lupus erythematosus. Infect Dis Clin Pract 1999; 8:225. [27] Kollef MH, Enzenauer RJ. Predicting outcome from intensive care for patients with rheumatologic diseases. J Rheumatol 1992;19:1260 2. [28] Lee P, Urowitz MB, Bookman AA, et al. Systemic lupus erythematosus. A review of 110 cases with reference to nephritis, the nervous system, infections, aseptic necrosis and prognosis. QJM 1977;46:1 32. [29] Mitchell DM, Spitz PW, Young DY, et al. Survival, prognosis, and causes of death in rheumatoid arthritis. Arthritis Rheum 1986;29:706 14. [30] Mok CC, Lee KW, Ho CT, et al. A prospective study of survival and prognostic indicators of systemic lupus erythematosus in a southern Chinese population. Rheumatology (Oxford) 2000; 39:399 406. [31] Myllykangas-Luosujarvi R, Aho K, Kautiainen H, et al. Shortening of life span and causes of excess mortality in a population-based series of subjects with rheumatoid arthritis. Clin Exp Rheumatol 1995;13:149 53. [32] Noel V, Lortholary O, Casassus P, et al. Risk factors and prognostic influence of infection in a single cohort of 87 adults with systemic lupus erythematosus. Ann Rheum Dis 2001;60: 1141 4. [33] Oh HM, Chng HH, Boey ML, et al. Infections in systemic lupus erythematosus. Singapore Med J 1993;34:406 8. [34] Paton NI. Infections in systemic lupus erythematosus patients. Ann Acad Med Singapore 1997;26:694 700. [35] Peschken CA, Esdaile JM. Systemic lupus erythematosus in North American Indians: a population based study. J Rheumatol 2000;27:1884 91. [36] Petri M. Infection in systemic lupus erythematosus. Rheum Dis Clin North Am 1998;24(2): 423 56. [37] Prior P, Symmons DP, Scott DL, et al. Cause of death in rheumatoid arthritis. Br J Rheumatol 1984;23:92 9. [38] Ramey DR, Rausch PI, Schettler JD, et al. Serious infections in rheumatoid arthritis: what is the scope of the problem? [abstract]. Arthritis Rheum 1999;42:S279. [39] Riise T, Jacobsen BK, Gran JT, et al. Total mortality is increased in rheumatoid arthritis. A 17-year prospective study. Clin Rheumatol 2001;20:123 7. [40] Rosner S, Ginzler EM, Diamond HS, et al. A multicenter study of outcome in systemic lupus erythematosus. II. causes of death. Arthritis Rheum 1982;25:612 7. [41] Rubin LA, Urowitz MB, Gladman DD. Mortality in systemic lupus erythematosus: the bimodal pattern revisited. QJM 1985;55:87 98. [42] Shyam C, Malaviya AN. Infection-related morbidity in systemic lupus erythematosus: a clinico-epidemiological study from northern India. Rheumatol Int 1996;16:1 3. [43] Stahl-Hallengren C, Jonsen A, Nived O, et al. Incidence studies of systemic lupus erythematosus in southern Sweden: increasing age, decreasing frequency of renal manifestations and good prognosis. J Rheumatol 2000;27:685 91. [44] Staples PJ, Gerding DN, Decker JL, et al. Incidence of infection in systemic lupus erythematosus. Arthritis Rheum 1974;17:1 10.
946
[45] Thong BY, Tai DY, Goh SK, et al. An audit of patients with rheumatic disease requiring medical intensive care. Ann Acad Med Singapore 2001;30:254 9. [46] Trager J, Ward MM. Mortality and causes of death in systemic lupus erythematosus. Curr Opin Rheumatol 2001;13:345 51. [47] Vandenbroucke JP, Hazevoet HM, Cats A. Survival and cause of death in rheumatoid arthritis: a 25-year prospective followup. J Rheumatol 1984;11:158 61. [48] Ward MM, Pyun E, Studenski S. Causes of death in systemic lupus erythematosus. Long-term followup of an inception cohort. Arthritis Rheum 1995;38:1492 9. [49] Wolfe F, Mitchell DM, Sibley JT, et al. The mortality of rheumatoid arthritis. Arthritis Rheum 1994;37:481 94. [50] Yeap SS, Chow SK, Manivasagar M, et al. Mortality patterns in Malaysian systemic lupus erythematosus patients. Med J Malaysia 2001;56:308 12. [51] Zonana-Nacach A, Camargo-Coronel A, Yanez P, Sanchez L, et al. Infections in outpatients with systemic lupus erythematosus: a prospective study. Lupus 2001;10:505 10. [52] Moore PM, Cupps TR. Neurological complications of vasculitis. Ann Neurol 1983;14:155 67. [53] Mraz-Gernhard SM, Bush TM, Riebman JB. Clinical images: Libman-Sacks endocarditis. Arthritis Rheum 2001;44:2111. [54] Vaughan JH. Infection and rheumatic diseases: a review (2). Bull Rheum Dis 1990;39:1 8. [55] Venables PJ. Infection and rheumatoid arthritis. Curr Opin Rheumatol 1989;1:15 20. [56] Cohen J, Pinching AJ, Rees AJ, et al. Infection and immunosuppression. A study of the infective complications of 75 patients with immunologically-mediated disease. QJM 1982; 51:1 15. [57] Go CHU, Cunha BA. Infections in patients on steroids. Infectious Disease Practice. 2000;24:61. [58] Klein NC, Go CH, Cunha BA. Infections associated with steroid use. Infect Dis Clin North Am 2001;15:423 32. [59] Mikuls TR, Saag KG. Comorbidity in rheumatoid arthritis. Rheum Dis Clin North Am 2001;27: 283 303. [60] Segal BH, Sneller MC. Infectious complications of immunosuppressive therapy in patients with rheumatic diseases. Rheum Dis Clin North Am 1997;23:219 37. [61] Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticosteroids. Review of Infectious Diseases 1989;11:954 63. [62] Aboguddah A, Stein HB, Phillips P, et al. Herpes simplex hepatitis in a patient with psoriatic arthritis taking prednisone and methotrexate. Report and review of the literature. J Rheumatol 1991;18:1406 12. [63] Auzary C, Mouthon L, Soilleux M, et al. Localized subcutaneous Nocardia farcinica abscess in a woman with overlap syndrome between systemic scleroderma and polymyositis. Ann Med Interne (Paris) 1999;150:582 4. [64] Badsha H, Edwards CJ, Chng HH. Melioidosis in systemic lupus erythematosus: the importance of early diagnosis and treatment in patients from endemic areas. Lupus 2001;10:821 3. [65] DiNubile MJ, Albornoz MA, Stumacher RJ, et al. Pneumococcal soft-tissue infections: possible association with connective tissue diseases. J Infect Dis 1991;163:897 900. [66] Galarza DA, Esquivel-Valerio JA, Navarro G, et al. Prevalence of chlamydia ocular infection in patients with rheumatoid arthritis who are taking glucocorticoids [abstract]. Arthritis Rheum 2001;44:S173. [67] Hellmann DB, Petri M, Whiting-OKeefe Q. Fatal infections in systemic lupus erythematosus: the role of opportunistic organisms. Medicine (Baltimore) 1987;66:341 8. [68] Kraus A, Cabral AR, Sifuentes-Osornio J, et al. Listeriosis in patients with connective tissue diseases. J Rheumatol 1994;21:635 8. [69] Ognibene FP, Shelhamer JH, Hoffman GS, et al. Pneumocystis carinii pneumonia: a major complication of immunosuppressive therapy in patients with Wegeners granulomatosis. Am J Respir Crit Care Med 1995;151:795 9. [70] Rivera E, Maldonado N, Velez-Garcia E, et al. Hyperinfection syndrome with Strongyloides stercoralis. Ann Intern Med 1970;72:199 204.
947
[71] Scowden EB, Schaffner W, Stone WJ. Overwhelming strongyloidiasis: an unappreciated opportunistic infection. Medicine (Baltimore) 1978;57:527 44. [72] Setoyama M, Fukumaru S, Takasaki T, et al. SLE with death from acute massive pulmonary hemorrhage caused by disseminated strongyloidiasis. Scand J Rheumatol 1997;26:389 91. [73] Van der Straeten C, Wei N, Rothschild J, et al. Rapidly fatal pneumococcal septicemia in systemic lupus erythematosus. J Rheumatol 1987;14:1177 80. [74] Wiggins Jr. RE. Invasive aspergillosis. A complication of treatment of temporal arteritis. J Neuroophthalmol 1995;15:36 8. [75] Wilcox MH, Powell RJ, Pugh SF, et al. Toxoplasmosis and systemic lupus erythematosus. Ann Rheum Dis 1990;49:254 7. [76] Andersen FG, Guckian JC. Systemic lupus erythematosus associated with fatal pulmonary coccidioidomycosis. Tex Rep Biol Med 1968;26:93 9. [77] Balbir-Gurman A, Schapira D, Nahir AM. Primary subcutaneous nocardial infection in a SLE patient. Lupus 1999;8:164 7. [78] Greene R, Kaufman R, Quismorio Jr. FP. Septic bursitis in systemic lupus erythematosus. Clin Rheumatol 1984;3:55 9. [79] Huang JW, Hung KY, Yen CJ, et al. Systemic lupus erythematosus and peritoneal dialysis: outcomes and infectious complications. Perit Dial Int 2001;21:143 7. [80] Gardner GC, Weisman MH. Pyarthrosis in patients with rheumatoid arthritis: a report of 13 cases and a review of the literature from the past 40 years. Am J Med 1990;88:503 11. [81] Doran MF, Pond GR, Crowson CS, et al. Risk of infection in persons with rheumatoid arthritis compared to controls: a population-based study [abstract]. Arthritis Rheum 2001; 44:S105. [82] Mowat AG, Hothersall TE, Gould JC. Urinary tract infection in patients with rheumatoid arthritis. Ann Rheum Dis 1970;29:143 8. [83] Myllykangas-Luosujarvi RA, Aho K, Isomaki HA. Mortality in rheumatoid arthritis. Semin Arthritis Rheum 1995;25:193 202. [84] Rowe IF, Deans AC, Keat AC. Pyogenic infection and rheumatoid arthritis. Postgrad Med J 1987;63:19. [85] Symmons DP, Jones MA, Scott DL, et al. Longterm mortality outcome in patients with rheumatoid arthritis: early presenters continue to do well. J Rheumatol 1998;25:1072 7. [86] Al-Hadithy H, Isenberg DA, Addison IE, et al. Neutrophil function in systemic lupus erythematosus and other collagen diseases. Ann Rheum Dis 1982;41:33 8. [87] Iliopoulos AG, Tsokos GC. Immunopathogenesis and spectrum of infections in systemic lupus erythematosus. Semin Arthritis Rheum 1996;25:318 36. [88] Ng WI, Yuen KY, Chu CM. Lymphopenia at disease presentation predicts major infections in patients with systemic lupus erythematosus [abstract]. Arthritis Rheum 2001;44:S 245. [89] Ehrenfeld M, Urowitz MB, Platts ME. Selective C4 deficiency, systemic lupus erythematosus, and Whipples disease. Ann Rheum Dis 1984;43:91 4. [90] Dillon AM, Stein HB, English RA. Splenic atrophy in systemic lupus erythematosus. Ann Intern Med 1982;96:40 3. [91] Piliero P, Furie R. Functional asplenia in systemic lupus erythematosus. Semin Arthritis Rheum 1990;20:185 9. [92] Austin III HA, Klippel JH, Balow JE, et al. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med 1986;314:614 9. [93] Seror P, Pluvinage P, dAndre FL, et al. Frequency of sepsis after local corticosteroid injection (an inquiry on 1160000 injections in rheumatological private practice in France). Rheumatology (Oxford) 1999;38:1272 4. [94] Fauci AS, Dale DC. The effect of in vivo hydrocortisone on subpopulations of human lymphocytes. J Clin Invest 1974;53:240 6. [95] Butler WT, Rossen RD. Effects of corticosteroids on immunity in man. I. decreased serum IgG concentration caused by 3 or 5 days of high doses of methylprednisolone. J Clin Invest 1973; 52:2629 40.
948
[96] Saag KG, Koehnke R, Caldwell JR, et al. Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med 1994;96:115 23. [97] Williams AJ, Zardawi I, Walls J. Disseminated aspergillosis in high dose steroid therapy. Lancet 1983;1:1222. [98] Wollheim FA. Acute and long-term complications of corticosteroid pulse therapy. Scand J Rheumatol Suppl 1984;54:27 32. [99] Badsha H, Kong KO, Lian TY, et al. Pulse methylprednisolone for SLE flares: a lower dose decreases the risk of serious infection without reducing efficacy [abstract]. Arthritis Rheum 2001;44:S280. [100] Laan RF, van Riel PL, van de Putte LB. Leflunomide and methotrexate. Curr Opin Rheumatol 2001;13:159 63. [101] Sneller MC, Hoffman GS, Talar-Williams C, et al. An analysis of forty-two Wegeners granulomatosis patients treated with methotrexate and prednisone. Arthritis Rheum 1995; 38:608 13. [102] McCune WJ, Golbus J, Zeldes W, et al. Clinical and immunologic effects of monthly administration of intravenous cyclophosphamide in severe systemic lupus erythematosus. N Engl J Med 1988;318:1423 31. [103] Bradley JD, Brandt KD, Katz BP. Infectious complications of cyclophosphamide treatment for vasculitis. Arthritis Rheum 1989;32:45 53. [104] Kattwinkel N, Cook L, Agnello V. Overwhelming fatal infection in a young woman after intravenous cyclophosphamide therapy for lupus nephritis. J Rheumatol 1991;18:79 81. [105] van der Veen MJ, van der Heide A, Kruize AA, et al. Infection rate and use of antibiotics in patients with rheumatoid arthritis treated with methotrexate. Ann Rheum Dis 1994;53:224 8. [106] Lang B, Riegel W, Peters T, et al. Low dose methotrexate therapy for rheumatoid arthritis complicated by pancytopenia and Pneumocystis carinii pneumonia. J Rheumatol 1991;18: 1257 9. [107] Smith JD, Knox JM. Psoriasis, methotrexate and tuberculosis. Br J Dermatol 1971;84:590 3. [108] Boerbooms AM, Kerstens PJ, van Loenhout JW, et al. Infections during low-dose methotrexate treatment in rheumatoid arthritis. Semin Arthritis Rheum 1995;24:411 21. [109] Perhala RS, Wilke WS, Clough JD, et al. Local infectious complications following large joint replacement in rheumatoid arthritis patients treated with methotrexate versus those not treated with methotrexate. Arthritis Rheum 1991;34:146 52. [110] Salaffi F, Manganelli P, Carotti M, et al. Methotrexate-induced pneumonitis in patients with rheumatoid arthritis and psoriatic arthritis: report of five cases and review of the literature. Clin Rheumatol 1997;16:296 304. [111] Anderson DJ, Janoff EN. Herpes zoster infection in a patient on methotrexate given prednisone to prevent post-herpetic neuralgia. Ann Intern Med 1987;107:783. [112] Antonelli MA, Moreland LW, Brick JE. Herpes zoster in patients with rheumatoid arthritis treated with weekly, low-dose methotrexate. Am J Med 1991;90:295 8. [113] Altz-Smith M, Kendall Jr. LG, Stamm AM. Cryptococcosis associated with low-dose methotrexate for arthritis. Am J Med 1987;83:179 81. [114] Furst DE, Erikson N, Clute L, et al. Adverse experience with methotrexate during 176 weeks of a longterm prospective trial in patients with rheumatoid arthritis. J Rheumatol 1990;17: 1628 35. [115] Gispen JG, Alarcon GS, Johnson JJ, et al. Toxicity of methotrexate in rheumatoid arthritis. J Rheumatol 1987;14:74 9. [116] Jansen TL, van Heereveld HA, Laan RF, et al. Septic arthritis with Listeria monocytogenes during low-dose methotrexate. J Intern Med 1998;244:87 90. [117] Keegan JM, Byrd JW. Nocardiosis associated with low dose methotrexate for rheumatoid arthritis. J Rheumatol 1988;15:1585 6. [118] Krugmann J, Sailer-Hock M, Muller T, et al. Epstein-Barr virus-associated Hodgkins lymphoma and legionella pneumophila infection complicating treatment of juvenile rheumatoid arthritis with methotrexate and cyclosporine A. Hum Pathol 2000;31:253 5.
949
[119] Wallace JR, Luchi M. Fatal cytomegalovirus pneumonia in a patient receiving corticosteroids and methotrexate for mixed connective tissue disease. South Med J 1996;89:726 8. [120] Witty LA, Steiner F, Curfman M, et al. Disseminated histoplasmosis in patients receiving lowdose methotrexate therapy for psoriasis. Arch Dermatol 1992;128:91 3. [121] Bridges Jr. SL, Lopez-Mendez A, Han KH, et al. Should methotrexate be discontinued before elective orthopedic surgery in patients with rheumatoid arthritis? J Rheumatol 1991;18:984 8. [122] Hargreaves MR, Mowat AG, Benson MK. Acute pneumonitis associated with low dose methotrexate treatment for rheumatoid arthritis: report of five cases and review of published reports. Thorax 1992;47:628 33. [123] Schreiber SL, Crabtree GR. The mechanism of action of cyclosporin A and FK506. Immunol Today 1992;13:136 42. [124] Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000;343:1586 93. [125] US Food and Drug Administration. Criteria for use of leflunamide, etanercept, and infliximab in the treatment of rheumatoid arthritis. U.S. Food and Drug Administration (Rockville, MD); 2001. Available at: http://vapbm.org/criteria/lef_etan_infcriteria.pdf. Accessed 1 Oct 2001. [126] Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001;345:1098 104. [127] Lipsky P, St Clair EW, Furst D. 54-week clinical and radiographic results from the ATTRACT trial: a Phase III study of infliximab (Remicade) in patients with active RA despite methotrexate [abstract]. Arthritis Rheum 1999;42(Suppl):S147. [128] Maini R, St Clair EW, Breedveld F, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet. 1999;354:1932 9. [129] Van den Bosch F, De Keyser F, Joos R, et al. Reactivation of tuberculosis in 2 patients with spondyloarthropathy treated with infliximab [abstract]. Arthritis Rheum 2001;44:S78. [130] Baghai M, Osmon DR, Wolk DM, et al. Fatal sepsis in a patient with rheumatoid arthritis treated with etanercept. Mayo Clin Proc 2001;76:653 6. [131] Belostocki KB, Leibowitz E, Tai K, et al. Infections associated with etanercept treatment of rheumatoid arthritis: 2 years of experience in the real-world[abstract]. Arthritis Rheum 2001; 44:S173. [132] Keenan GF, Clark J, Baker DG, et al. The rare occurrence of fungal infections in patients receiving infliximab [abstract]. Arthritis Rheum 2001;44:S82. [133] Wallis WJ, Burge DJ, Sabath D, et al. Tuberculosis reports with etanercept (Enbrel1) therapy [abstract]. Arthritis Rheum 2001;44:S78. [134] Carmona L, Gonzalez-Alvaro I, Sanmarti R, et al. EMECAR Study Group. Rheumatoid arthritis is associated to a four-fold increase in tuberculosis infection incidence in the pre-biologics era [abstract]. Arthritis Rheum 2001;44:S173. [135] Harvey AM, Shulman LE, Tumulty PA, et al. Systemic lupus erythematosus: review of the literature and clinical analysis of 138 cases. Medicine (Baltimore) 1954;33:291 437. [136] Inoue T, Takeda T, Koda S, et al. Differential diagnosis of fever in systemic lupus erythematosus using discriminant analysis. Rheumatol Int 1986;6:69 77. [137] Stahl NI, Klippel JH, Decker JL. Fever in systemic lupus erythematosus. Am J Med 1979;67: 935 40. [138] Kim JS, Lee KS, Koh EM, et al. Thoracic involvement of systemic lupus erythematosus: clinical, pathologic, and radiologic findings. J Comput Assist Tomogr 2000;24:9 18. [139] Kim WU, Kim SI, Yoo WH, et al. Adult respiratory distress syndrome in systemic lupus erythematosus: causes and prognostic factors: a single center, retrospective study. Lupus 1999;8:552 7. [140] Donadio Jr. JV, Holley KE, Ferguson RH, et al. Treatment of diffuse proliferative lupus nephritis with prednisone and combined prednisone and cyclophosphamide. N Engl J Med 1978;299: 1151 5.
950
[141] Koch CA, Robyn JA, Coccia MR. Systemic lupus erythematosus: a risk factor for pneumonia caused by Legionella micdadei? Arch Intern Med 1997;157:2670 1. [142] Pohl MA, Lan SP, Berl T. Plasmapheresis does not increase the risk for infection in immunosuppressed patients with severe lupus nephritis. The Lupus Nephritis Collaborative Study Group. Ann Intern Med 1991;114:924 9. [143] Kraus A, Guerra-Bautista G, Chavarria P. Paragonimiasis: an infrequent but treatable cause of hemoptysis in systemic lupus erythematosus. J Rheumatol 1990;17:244 6. [144] Cheema GS, Quismorio Jr. FP. Interstitial lung disease in systemic lupus erythematosus. Curr Opin Pulm Med 2000;6:424 9. [145] Keane MP, Lynch III JP. Pleuropulmonary manifestations of systemic lupus erythematosus. Thorax 2000;55:159 66. [146] Orens JB, Martinez FJ, Lynch III JP. Pleuropulmonary manifestations of systemic lupus erythematosus. Rheum Dis Clin North Am 1994;20:159 93. [147] Prakash UB. Respiratory complications in mixed connective tissue disease. Clin Chest Med 1998;19:733 46. [148] Staudinger T, Roggla M, Kettenbach J, et al. Respiratory failure in systemic lupus erythematosus: decisive differentiation between acute pneumonitis and infection. Br J Rheumatol 1997;36:295 7. [149] Garrett DO, Jochimsen E, Jarvis W. Invasive Aspergillus spp infections in rheumatology patients. J Rheumatol 1999;26:146 9. [150] Mera JR, Whimbey E, Elting L, et al. Cytomegalovirus pneumonia in adult nontransplantation patients with cancer: review of 20 cases occurring from 1964 through 1990. Clin Infect Dis 1996;22:1046 50. [151] Nishino H, Rubino FA, DeRemee RA, et al. Neurological involvement in Wegeners granulomatosis: an analysis of 324 consecutive patients at the Mayo Clinic. Ann Neurol 1993;33:4 9. [152] Zamir D, Amar M, Groisman G, et al. Toxoplasma infection in systemic lupus erythematosus mimicking lupus cerebritis. Mayo Clin Proc 1999;74:575 8. [153] West SG. Neuropsychiatric lupus. Rheum Dis Clin North Am 1994;20:129 58. [154] Wong KL, Woo EK, Yu YL, et al. Neurological manifestations of systemic lupus erythematosus: a prospective study. QJM 1991;81:857 70. [155] Feinglass EJ, Arnett FC, Dorsch CA, et al. Neuropsychiatric manifestations of systemic lupus erythematosus: diagnosis, clinical spectrum, and relationship to other features of the disease. Medicine (Baltimore) 1976;55:323 39. [156] Sibley JT, Olszynski WP, Decoteau WE, et al. The incidence and prognosis of central nervous system disease in systemic lupus erythematosus. J Rheumatol 1992;19:47 52. [157] Suh CH, Jeong YS, Park HC, et al. Risk factors for infection and role of C-reactive protein in Korean patients with systemic lupus erythematosus. Clin Exp Rheumatol 2001;19:191 4. [158] Becker GJ, Waldburger M, Hughes GR, et al. Value of serum C-reactive protein measurement in the investigation of fever in systemic lupus erythematosus. Ann Rheum Dis 1980;39:50 2. [159] Hind CR, Ng SC, Feng PH, et al. Serum C-reactive protein measurement in the detection of intercurrent infection in Oriental patients with systemic lupus erythematosus. Ann Rheum Dis 1985;44:260 1. [160] Linares LF, Gomez-Reino JJ, Carreira PE, et al. C-reactive protein (CRP) levels in systemic lupus erythematosus (SLE). Clin Rheumatol 1986;5:66 9. [161] ter Borg EJ, Horst G, Limburg PC, et al. C-reactive protein levels during disease exacerbations and infections in systemic lupus erythematosus: a prospective longitudinal study. J Rheumatol 1990;17:1642 8. [162] Roy S, Tan KT. Pyrexia and normal C-reactive protein (CRP) in patients with systemic lupus erythematosus: always consider the possibility of infection in febrile patients with systemic lupus erythematosus regardless of CRP levels. Rheumatology (Oxford) 2001;40:349 50. [163] Liou LB. Serum and in vitro production of IL-1 receptor antagonist correlate with C-reactive protein levels in newly diagnosed, untreated lupus patients. Clin Exp Rheumatol 2001;19: 515 23.
951
[164] Lim MK, Lee CK, Ju YS, et al. Serum ferritin as a serologic marker of activity in systemic lupus erythematosus. Rheumatol Int 2001;20:89 93. [165] Ames PR, Alves J, Pap AF, et al. Fibrinogen in systemic lupus erythematosus: more than an acute phase reactant? J Rheumatol 2000;27:1190 5. [166] Shin KC, Lee YJ, Kang SW, et al. Serum procalcitonin measurement for detection of intercurrent infection in febrile patients with SLE. Ann Rheum Dis 2001;60:988 9. [167] Blanco FJ, Gomez-Reino JJ, de la Mata J, et al. Survival analysis of 306 European Spanish patients with systemic lupus erythematosus. Lupus 1998;7:159 63. [168] Jindal B, Joshi K, Radotra BD, et al. Fatal complications of systemic lupus erythematosus an autopsy study from north India. Indian J Pathol Microbiol 2000;43:311 7. [169] Kim WU, Min JK, Lee SH, et al. Causes of death in Korean patients with systemic lupus erythematosus: a single center retrospective study. Clin Exp Rheumatol 1999;17: 539 45. [170] Nived O, Sturfelt G, Wollheim F. Systemic lupus erythematosus and infection: a controlled and prospective study including an epidemiological group. QJM 1985;55:271 87. [171] Caldeira L, Dutschmann L, Carmo G, et al. Fatal Pasteurella multocida infection in a systemic lupus erythematosus patient. Infection 1993;21:254 5. [172] Deleze M, Mintz G, del Carmen Mejia M. Toxoplasma gondii encephalitis in systemic lupus erythematosus. A neglected cause of treatable nervous system infection. J Rheumatol 1985; 12:994 6. [173] Goodman SM, Russell L, Kagen L, et al. Fever and pneumonia in a steroid treated patient with systemic lupus erythematosus. Lupus 2000;9:318 21. [174] Rahman P, Gladman DD, Ibanez D, et al. Significance of isolated hematuria and isolated pyuria in systemic lupus erythematosus. Lupus 2001;10:418 23. [175] Clough W, Cassell GH, Duffy LB, et al. Septic arthritis and bacteremia due to Mycoplasma resistant to antimicrobial therapy in a patient with systemic lupus erythematosus. Clin Infect Dis 1992;15:402 7. [176] DErcole C, Boubli L, Franck J, et al. Recurrent congenital toxoplasmosis in a woman with lupus erythematosus. Prenat Diagn 1995;15:1171 5. [177] Molnar-Nadasdy G, Haesly I, Reed J, et al. Placental cryptococcosis in a mother with systemic lupus erythematosus. Arch Pathol Lab Med 1994;118:757 9. [178] Nomura S, Hatta K, Iwata T, et al. Legionella pneumophila isolated in pure culture from the ascites of a patient with systemic lupus erythematosus. Am J Med 1989;86:833 4. [179] Senecal JL, St-Antoine P, Beliveau C. Legionella pneumophila lung abscess in a patient with systemic lupus erythematosus. Am J Med Sci 1987;293:309 14. [180] Tai ES, Fong KY. Fatal amoebic colitis in a patient with SLE: a case report and review of the literature. Lupus 1997;6:610 2. [181] Gonzalez-Crespo MR, Gomez-Reino JJ. Invasive aspergillosis in systemic lupus erythematosus. Semin Arthritis Rheum 1995;24:304 14. [182] Abramson S, Kramer SB, Radin A, et al. Salmonella bacteremia in systemic lupus erythematosus. Eight-year experience at a municipal hospital. Arthritis Rheum 1985;28:75 9. [183] Mitchell SR, Nguyen PQ, Katz P. Increased risk of neisserial infections in systemic lupus erythematosus. Semin Arthritis Rheum 1990;20:174 84. [184] Shahram F, Akbarian M, Davatchi F. Salmonella infection in systemic lupus erythematosus. Lupus 1993;2:55 9. [185] Gorevic PD, Katler EI, Agus B. Pulmonary nocardiosis. Occurrence in men with systemic lupus erythematosus. Arch Intern Med 1980;140:361 3. [186] Ishibashi Y, Watanabe R, Hommura S, et al. Endogenous Nocardia asteroides endophthalmitis in a patient with systemic lupus erythematosus. Br J Ophthalmol 1990;74:433 6. [187] Mok CC, Lau CS, Poon SP. Primary nocardial meningitis in systemic lupus erythematosus. Br J Rheumatol 1995;34:178 81. [188] Mok CC, Lau CS, Yuen KY. Cryptococcal meningitis presenting concurrently with systemic lupus erythematosus. Clin Exp Rheumatol 1998;16:169 71.
952
[189] Petri M, Katzenstein P, Hellmann D. Laryngeal infection in lupus: report of nocardiosis and review of laryngeal involvement in lupus. J Rheumatol 1988;15:1014 5. [190] Zimmermann III B, Spiegel M, Lally EV. Cryptococcal meningitis in systemic lupus erythematosus. Semin Arthritis Rheum 1992;22:18 24. [191] Shatley MJ, Walker BL, McMurray RW. Lues and lupus: syphilis mimicking systemic lupus erythematosus (SLE). Lupus 2001;10:299 303. [192] Pryor BD, Bologna SG, Kahl LE. Risk factors for serious infection during treatment with cyclophosphamide and high-dose corticosteroids for systemic lupus erythematosus. Arthritis Rheum 1996;39:1475 82. [193] Yuhara T, Takemura H, Akama T, et al. Predicting infection in hospitalized patients with systemic lupus erythematosus. Intern Med 1996;35:629 36. [194] Gaubitz M, Herrmann M, Shahin M, et al. Cat scratch disease (bartonellosis) mimicking an SLE flare. Lupus 2001;10:883 5. [195] Huang YC, Lin YT, Yang YH, et al. Acute lupus pneumonitis mimicking pulmonary tuberculosis: a case report. J Microbiol Immunol Infect 2001;34:143 6. [196] Navarrete MG, Brey RL. Neuropsychiatric systemic lupus erythematosus. Current Treatment Options in Neurology 2000;2:473 85. [197] Ruggieri AP. Neuropsychiatric lupus: nomenclature, classification, criteria, and other confusional states. Arthritis Rheum 2001;45:406 9. [198] Gaylis NB, Altman RD, Ostrov S, Quencer R. The selective value of computed tomography of the brain in cerebritis due to systemic lupus erythematosus. J Rheumatol 1982;9:850 4. [199] Harisdangkul V, Songcharoen S, Lin AC. Listerial infections in patients with systemic lupus erythematosus. South Med J 1992;85:957 60. [200] Huseyin TS, Maynard JP, Leach RD. Toxic shock syndrome in a patient with breast cancer and systemic lupus erythematosus. Eur J Surg Oncol 2001;27:330 1. [201] Petros D, West S. Overwhelming pneumococcal bacteraemia in systemic lupus erythematosus. Ann Rheum Dis 1989;48:333 5. [202] Mackenzie AR, Laing RB, MacDonald AG, et al. Pneumococcal septicaemia in a patient with systemic lupus erythematosus. Ann Rheum Dis 1997;56:403 4. [203] Shalit M, Gross DJ, Levo Y. Pneumococcal epiglottitis in systemic lupus erythematosus on high-dose corticosteroids. Ann Rheum Dis 1982;41:615 6. [204] Webster J, Williams BD, Smith AP, et al. Systemic lupus erythematosus presenting as pneumococcal septicaemia and septic arthritis. Ann Rheum Dis 1990;49:181 3. [205] Boey ML, Feng PH. Salmonella infection in systemic lupus erythematosus. Singapore Med J 1982;23:147 51. [206] Chen JY, Luo SF, Wu YJ, et al. Salmonella septic arthritis in systemic lupus erythematosus and other systemic diseases. Clin Rheumatol 1998;17:282 7. [207] Pablos JL, Aragon A, Gomez-Reino JJ. Salmonellosis and systemic lupus erythematosus. Report of ten cases. Br J Rheumatol 1994;33:129 32. [208] Shamiss A, Thaler M, Nussinovitch N, et al. Multiple Salmonella enteritidis leg abscesses in a patient with systemic lupus erythematosus. Postgrad Med J 1990;66:486 8. [209] Lim E, Koh WH, Loh SF, et al. Non-typhoidal salmonellosis in patients with systemic lupus erythematosus. A study of fifty patients and a review of the literature. Lupus 2001;10: 87 92. [210] Lovy MR, Ryan PF, Hughes GR. Concurrent systemic lupus erythematosus and salmonellosis. J Rheumatol 1981;8:605 12. [211] van de Laar MA, Meenhorst PL, van Soesbergen RM, et al. Polyarticular Salmonella bacterial arthritis in a patient with systemic lupus erythematosus. J Rheumatol 1989;16:231 4. [212] Frayha RA, Jizi I, Saadeh G. Salmonella typhimurium bacteriuria. An increased infection rate in systemic lupus erythematosus. Arch Intern Med 1985;145:645 7. [213] Picillo U. Italian G, Marcialis MR, et al. Bilateral femoral osteomyelitis with knee arthritis due to Salmonella enteritidis in a patient with systemic lupus erythematosus. Clin Rheumatol 2001;20:53 6.
953
[214] Sanchez-Guerrero J, Alarcon-Segovia D. Salmonella pericarditis with tamponade in systemic lupus erythematosus. Br J Rheumatol 1990;29:69 71. [215] Li EK, Cohen MG, Ho AK, et al. Salmonella bacteremia occurring concurrently with the first presentation of systemic lupus erythematosus. Br J Rheumatol 1993;32:66 7. [216] Medina F, Fraga A, Lavalle C. Salmonella septic arthritis in systemic lupus erythematosus. The importance of chronic carrier state. J Rheumatol 1989;16:203 8. [217] Carratala J, Moreno R, Cabellos C, et al. Neisseria meningiditis monoarthritis revealing systemic lupus erythematosus. J Rheumatol 1988;15:532 3. [218] Feliciano R, Swedler W, Varga J. Infection with uncommon subgroup Y Neisseria meningitidis in patients with systemic lupus erythematosus. Clin Exp Rheumatol 1999;17:737 40. [219] Lehman TJ, Bernstein B, Hanson V, et al. Meningococcal infection complicating systemic lupus erythematosus. J Pediatr 1981;99:94 6. [220] Tikly M, Diese M, Zannettou N, et al. Gonococcal endocarditis in a patient with systemic lupus erythematosus. Br J Rheumatol 1997;36:270 2. [221] Turner-Stokes L, Isenberg DA. Immunisation of patients with rheumatoid arthritis and systemic lupus erythematosus. Ann Rheum Dis 1988;47:529 31. [222] Kim HA, Yoo CD, Baek HJ, et al. Mycobacterium tuberculosis infection in a corticosteroidtreated rheumatic disease patient population. Clin Exp Rheumatol 1998;16:9 13. [223] Kim HY, Im JG, Goo JM, et al. Pulmonary tuberculosis in patients with systematic lupus erythematosus. AJR Am J Roentgenol 1999;173:1639 42. [224] Tam LS, Li, EK, Szeto CC. Tuberculosis in Chinese patients with systemic lupus erythematosus [abstract]. Arthritis Rheum 2001;44:S245. [225] Victorio-Navarra STG, Arroyo CG, Torralba TP. Tuberculosis among Filipino patients with systemic lupus erythematosus. Lupus 1995;4(S2):89. [226] Belzunegui J, Plazaola I, Uriarte E, et al. Primary tuberculous muscle abscess in a patient with systemic lupus erythematosus. Br J Rheumatol 1995;34:1177 8. [227] Berker M, Atalay B, Soylemezoglu F, et al. Cervical tuberculous spondylitis associated with systemic lupus erythematosus. Spinal Cord 2001;39:549 53. [228] Uthman I, Bizri AR, Hajj AR, et al. Miliary tuberculosis presenting as tenosynovitis in a case of rheumatoid arthritis. J Infect 1998;37:196 8. [229] Feng PH, Tan TH. Tuberculosis in patients with systemic lupus erythematosus. Ann Rheum Dis 1982;41:11 4. [230] Hernandez-Cruz B, Sifuentes-Osornio J, Ponce-de-Leon Rosales S, et al. Mycobacterium tuberculosis infection in patients with systemic rheumatic diseases. A case-series. Clin Exp Rheumatol 1999;17:289 96. [231] Czelusta A, Moore AY. Cutaneous Mycobacterium kansasii infection in a patient with systemic lupus erythematosus: case report and review. J Am Acad Dermatol 1999;40:359 63. [232] Glickstein SL, Nashel DJ. Mycobacterium kansasii septic arthritis complicating rheumatic disease: case report and review of the literature. Semin Arthritis Rheum 1987;16:231 5. [233] Nakamura T, Yamamura Y, Tsuruta T, et al. Mycobacterium kansasii arthritis of the foot in a patient with systemic lupus erythematosus. Intern Med 2001;40:1045 9. [234] Sarrot-Reynauld F, Massot C, Dupre A. Ileo-caecal tuberculosis in systemic lupus erythematosus. Lupus 1995;4(S2):88. [235] Zvetina JR, Demos TC, Rubinstein H. Mycobacterium intracellulare infection of the shoulder and spine in a patient with steroid-treated systemic lupus erythematosus. Skeletal Radiol 1982;8:111 3. [236] Kruyswijk MR, Keuning JJ. Cutaneous cryptococcosis in a patient receiving immunosuppressive drugs for systemic lupus erythematosus. Dermatologica 1980;161:280 4. [237] Nenoff P, Horn LC, Mierzwa M, et al. Peracute disseminated fatal Aspergillus fumigatus sepsis as a complication of corticoid-treated systemic lupus erythematosus. Mycoses 1995;38: 467 71. [238] Pillay VK, Wilson DM, Ing TS, et al. Fungus infection in steroid-treated systemic lupus erythematosus. JAMA 1968;205:261 5.
954
[239] Sato M, Saku N, Takeda A, et al. A case report pulmonary cryptococcosis associated with systemic lupus erythematosus and review of 44 cases in Japan. Ryumachi 1993;33:56 62. [240] Collazos J, Martinez E, Flores M, et al. Aspergillus pneumonia successfully treated with itraconazole in a patient with systemic lupus erythematosus. Clin Investig Med 1994;72:920 1. [241] Fingerote RJ, Seigel S, Atkinson MH, et al. Disseminated zygomycosis associated with systemic lupus erythematosus. J Rheumatol 1990;17:1692 4. [242] Hansen KE, St Clair EW. Disseminated histoplasmosis in systemic lupus erythematosus: case report and review of the literature. Semin Arthritis Rheum 1998;28:193 9. [243] Katz A, Ehrenfeld M, Livneh A., et al. Aspergillosis in systemic lupus erythematosus. Semin Arthritis Rheum 1996;26:635 40. [244] Lo CY, Chan DT, Yuen KY, et al. Penicillium marneffei infection in a patient with SLE. Lupus 1995;4:229 31. [245] Sawada M, Isogai S, Miyake S, et al. Pulmonary pseudallescherioma associated with systemic lupus erythematosus. Intern Med 1998;37:1046 9. [246] Sieving RR, Kauffman CA, Watanakunakorn C. Deep fungal infection in systemic lupus erythematosus three cases reported, literature reviewed. J Rheumatol 1975;2:61 72. [247] Yorgin PD, Rewari M, al-Uzri AY, et al. Coccidioidomycosis in adolescents with lupus nephritis. Pediatr Nephrol 2001;16:77 81. [248] Chayakul P, Thammakumpee G, Mitarnun W. Lung cavities from Pneumocystis carinii in a patient with systemic lupus erythematosus. J Med Assoc Thai 1991;74:310 2. [249] Fortenberry JD, Shew ML. Fatal Pneumocystis carinii in an adolescent with systemic lupus erythematosus. J Adolesc Health Care 1989;10:570 2. [250] Liam CK, Wang F. Pneumocystis carinii pneumonia in patients with systemic lupus erythematosus. Lupus 1992;1:379 85. [251] Page B. Pneumocystis carinii pneumonia and systemic lupus erythematosus. Lupus 1995;4:89. [252] Porges AJ, Beattie SL, Ritchlin C. Patients with systemic lupus erythematosus at risk for Pneumocystis carinii pneumonia. J Rheumatol 1992;19:1191 4. [253] Sharma CP, Chaudhary D, Behera D. Pneumocystis carinii pneumonia in a patient with active untreated systemic lupus erythematosus. Indian J Chest Dis Allied Sci 2001;43:169 71. [254] Tsai HC, Lee SS, Lin HH, et al. Pneumocystis carinii pneumonia in systemic lupus erythematosus: a report of two cases. J Formos Med Assoc 2001;100:699 702. [255] Gerrard JG. Pneumocystis carinii pneumonia in HIV-negative immunocompromised adults. Med J Aust 1995;162:233 5. [256] Kadoya A, Okada J, Iikuni Y, et al. Risk factors for Pneumocystis carinii pneumonia in patients with polymyositis/dermatomyositis or systemic lupus erythematosus. J Rheumatol 1996;23: 1186 8. [257] Ward MM, Donald F. Pneumocystis carinii pneumonia in patients with connective tissue diseases: the role of hospital experience in diagnosis and mortality. Arthritis Rheum 1999; 42:780 9. [258] Godeau B, Coutant-Perronne V, Le Thi Huong D, et al. Pneumocystis carinii pneumonia in the course of connective tissue disease: report of 34 cases. J Rheumatol 1994;21:246 51. [259] Permin H, Aldershvile J, Nielsen JO. Hepatitis B virus infection in patients with rheumatic diseases. Ann Rheum Dis 1982;41:479 82. [260] Ramos-Casals M, Font J, Garcia-Carrasco M, et al. Hepatitis C virus infection mimicking systemic lupus erythematosus: study of hepatitis C virus infection in a series of 134 Spanish patients with systemic lupus erythematosus. Arthritis Rheum 2000;43:2801 6. [261] Kahl LE. Herpes zoster infections in systemic lupus erythematosus: risk factors and outcome. J Rheumatol 1994;21:84 6. [262] Kang TY, Jun JB, Jung S, et al. Herpes zoster infection in patients with systemic lupus erythematosus [abstract]. Arthritis Rheum 2001;44:S245. [263] Moga I, Formiga F, Canet R, et al. Herpes-zoster virus infection in patients with systemic lupus erythematosus. Rev Clin Esp 1995;195:530 3. [264] Bendiksen S, Van Ghelue M, Rekvig OP, et al. A longitudinal study of human cytomegalovirus
955
[265] [266] [267] [268] [269] [270] [271]
[272] [273] [274] [275] [276] [277] [278] [279] [280] [281]
[282] [283] [284] [285] [286] [287] [288]
serology and viruria fails to detect active viral infection in 20 systemic lupus erythematosus patients. Lupus 2000;9:120 6. Rider JR, Ollier WE, Lock RJ, et al. Human cytomegalovirus infection and systemic lupus erythematosus. Clin Exp Rheumatol 1997;15:405 9. Vasquez V, Barzaga RA, Cunha BA. Cytomegalovirus-induced flare of systemic lupus erythematosus. Heart Lung 1992;21:407 8. Dror Y, Blachar Y, Cohen P, et al. Systemic lupus erythematosus associated with acute EpsteinBarr virus infection. Am J Kidney Dis 1998;32:825 8. Hayashi T, Lee S, Ogasawara H, et al. Exacerbation of systemic lupus erythematosus related to cytomegalovirus infection. Lupus 1998;7:561 4. Krueger GR, Sander C, Hoffmann A, et al. Isolation of human herpesvirus-6 (HHV-6) from patients with collagen vascular diseases. In Vivo 1991;5:217 25. Tokunaga Y, Takenaka K, Asayama R, et al. Cytomegalovirus-induced interstitial pneumonitis in a patient with systemic lupus erythematosus. Intern Med 1996;35:517 20. Vilaichone RK, Mahachai V, Eiam-Ong S, et al. Necrotizing ileitis caused by cytomegalovirus in patient with systemic lupus erythematosus: case report. J Med Assoc Thai 2001;84(Suppl 1): S469 73. Fox RA, Isenberg DA. Human immunodeficiency virus infection in systemic lupus erythematosus. Arthritis Rheum 1997;40:1168 72. Newton P, Aldridge RD, Lessells AM, et al. Progressive multifocal leukoencephalopathy complicating systemic lupus erythematosus. Arthritis Rheum 1986;29:337 43. Ferri C, Zakrzewska K, Longombardo G, et al. Parvovirus B19 infection of bone marrow in systemic sclerosis patients. Clin Exp Rheumatol 1999;17:718 20. Vigeant P, Menard HA, Boire G. Chronic modulation of the autoimmune response following parvovirus B19 infection. J Rheumatol 1994;21:1165 7. Hsu TC, Tsay GJ. Human parvovirus B19 infection in patients with systemic lupus erythematosus. Rheumatology (Oxford) 2001;40:152 7. Narvaez Garcia FJ, Domingo-Domenech E, Castro-Bohorquez FJ, et al. Lupus-like presentation of parvovirus B19 infection. Am J Med 2001;111:573 5. Caramaschi P, Zeminian S, Carletto A, et al. Parvovirus B19 infection and rheumatic diseases. Rev Rhum Engl Ed 1996;63:846 53. Chassagne P, Mejjad O, Gourmelen O, et al. Exacerbation of systemic lupus erythematosus during human parvovirus B19 infection. Br J Rheumatol 1993;32:158 9. Nigro G, Piazze J, Taliani G, et al. Postpartum lupus erythematosus associated with parvovirus B19 infection. J Rheumatol 1997;24:968 70. van Albada-Kuipers GA, Linthorst J, Peeters EA, et al. Frequency of infection among patients with rheumatoid arthritis versus patients with osteoarthritis or soft tissue rheumatism. Arthritis Rheum 1988;31:667 71. Vandenbroucke JP, Kaaks R, Valkenburg HA, et al. Frequency of infections among rheumatoid arthritis patients, before and after disease onset. Arthritis Rheum 1987;30:810 3. Goldenberg DL. Infectious arthritis complicating rheumatoid arthritis and other chronic rheumatic disorders. Arthritis Rheum 1989;32:496 502. Mateo Soria L, Miquel Nolla Sole J, Rozadilla Sacanell A, et al. Infectious arthritis in patients with rheumatoid arthritis. Ann Rheum Dis 1992;51:402 3. Mitchell WS, Brooks PM, Stevenson RD, et al. Septic arthritis in patients with rheumatoid disease: a still underdiagnosed complication. J Rheumatol 1976;3:124 33. Nolla JM, Gomez-Vaquero C, Fiter J, et al. Pyarthrosis in patients with rheumatoid arthritis: a detailed analysis of 10 cases and literature review. Semin Arthritis Rheum 2000;30:121 6. Sharma M, Leirisalo-Repo M. Arthritis patient as an emergency case at a university hospital. Scand J Rheumatol 1997;26:30 6. Dubost JJ, Fis I, Soubrier M, et al. Septic arthritis in rheumatoid arthritis. A review of twenty-four cases of the medical literature. Revue du Rhumatisme Edition Francaise 1994; 61:143 65.
956
[289] Kellgren J, Ball J, Fairbrother R, et al. Suppurative arthritis complicating rheumatoid arthritis. BMJ 1958;1:1193. [290] Kraft SM, Panush RS, Longley S. Unrecognized staphylococcal pyarthrosis with rheumatoid arthritis. Semin Arthritis Rheum 1985;14:196 201. [291] Barth WF, Healey LA, Decker JL. Septic arthritis due to Pasteurella multocida complicating rheumatoid arthritis. Arthritis Rheum 1968;11:394 9. [292] Campen DH, Kaufman RL, Beardmore TD. Candida septic arthritis in rheumatoid arthritis. J Rheumatol 1990;17:86 8. [293] Dodd MJ, Griffiths ID, Freeman R. Pyogenic arthritis due to bacteroides complicating rheumatoid arthritis. Ann Rheum Dis 1982;41:248 9. [294] Duyur B, Erdem HR, Ozgocmen S. Paravertebral abscess formation and knee arthritis due to brucellosis in a patient with rheumatoid arthritis. Spinal Cord 2001;39:554 6. [295] Gordon DL, Philpot CR, McGuire C. Plesiomonas shigelloides septic arthritis complicating rheumatoid arthritis. Aust N Z J Med 1983;13:275 6. [296] Gruberg L, Thaler M, Rozenman J, et al. Nocardia asteroides infection complicating rheumatoid arthritis. J Rheumatol 1991;18:459 61. [297] Iwata H, Kinoshita M, Sumiya M, et al. Emergence of erosive polyarthritis coincident with Mycobacterium kansasii pulmonary infection in a patient with systemic sclerosis-rheumatoid arthritis overlap syndrome. Clin Exp Rheumatol 1999;17:757 8. [298] Jeansson S, Kvien TK. Acanthamoeba polyphaga in rheumatoid arthritis: possibility for a chronic infection. Scand J Immunol 2001;53:610 4. [299] Brzeski M, Smart L, Baird D, et al. Pneumococcal septic arthritis after splenectomy in Feltys syndrome. Ann Rheum Dis 1991;50:724 6. [300] Gonzalez-Gay MA, Fernandez Camblor B, Varela E, et al. Septic arthritis from Streptococcus pneumoniae in rheumatoid arthritis. An Med Interna 1992;9:312. [301] Lohse A, Despaux J, Auge B, et al. Pneumococcal polyarticular septic arthritis in a patient with rheumatoid arthritis. Rev Rhum Engl Ed 1999;66:344 6. [302] Blackburn Jr. WD, Dunn TL, Alarcon GS. Infection versus disease activity in rheumatoid arthritis: eight years experience. South Med J 1986;79:1238 41. [303] Cornelissen JJ, Bakker LJ, Van der Veen MJ, et al. Nocardia asteroides pneumonia complicating low dose methotrexate treatment of refractory rheumatoid arthritis. Ann Rheum Dis 1991; 50:642 4. [304] Walker WC. Pulmonary infections and rheumatoid arthritis. QJM 1967;36:239 51. [305] Flood DA, Chan CK, Pruzanski W. Pneumocystis carinii pneumonia associated with methotrexate therapy in rheumatoid arthritis. J Rheumatol 1991;18:1254 6. [306] Perruquet JL, Harrington TM, Davis DE. Pneumocystis carinii pneumonia following methotrexate therapy for rheumatoid arthritis. Arthritis Rheum 1983;26:1291 2. [307] Roux N, Flipo RM, Cortet B, et al. Pneumocystis carinii pneumonia in rheumatoid arthritis patients treated with methotrexate. A report of two cases. Rev Rhum Engl Ed 1996;63:453 6. [308] Watkin SW, Bucknall RC, Nisar M, et al. Atypical mycobacterial infection of the lung in rheumatoid arthritis. Ann Rheum Dis 1989;48:336 8. [309] Wolfe F, Flowers N, Anderson J, et al. Tuberculosis rates are not increased in rheumatoid arthritis [abstract]. Arthritis Rheum 2001;44:S105. [310] Elkayam O, Paran D, Caspi D, et al. Immunogenicity and safety of pneumococcal vaccination in patients with rheumatoid arthritis or systemic lupus erythematosus. Clin Infect Dis 2002;34: 147 53. [311] Ioannou Y, Isenberg DA. Immunisation of patients with systemic lupus erythematosus: the current state of play. Lupus 1999;8:497 501.

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Crit Care Clin 18 (2002) 931 956

Infections in the immunocompromised rheumatologic patient

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

Defective cell-mediated immunity

Defective humoral immunity

Histoplasma capsulatum Coccidioides immitis Cryptococcus neoformans

Pneumocystic carinii Toxoplasma gondii Strongyloides stercoralis

Cytomegalovirus Epstein-Barr virus Varicella-Zoster virus

Streptococcus pneumoniae Haemophilus influenzae

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

Nodules or nodular infiltrates

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

[265] [266] [267] [268] [269] [270] [271]

[282] [283] [284] [285] [286] [287] [288]

S.B. Greenberg / Crit Care Clin 18 (2002) 931956

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