THERAPY IN PRACTICE

Am J Clin Dermatol 2003; 4 (3): 177-188

1175-0561/03/0003-0177/$30.00/0
Adis International Limited. All rights reserved.

HIV-Associated Pruritus
Etiology and Management
Fiza Singh and Donald Rudikoff
Mount Sinai Medical School of Medicine, New York, New York, USA

Contents
Abstract
. . . . . . . . . . . . . . . . . . . .
1. Infections and Infestations . . . . . . . . . . .
2. Non-Infectious Skin Diseases . . . . . . . . . .
2.1 Atopic-Like Dermatitis . . . . . . . . . . .
2.2 Psoriasis . . . . . . . . . . . . . . . . . . .
2.3 Seborrheic Dermatitis . . . . . . . . . . .
2.4 Pruritic Papular Eruptions . . . . . . . . .
2.5 Eosinophilic Folliculitis . . . . . . . . . . .
2.6 Prurigo Nodularis . . . . . . . . . . . . . .
3. Miscellaneous Causes of Pruritus . . . . . . .
3.1 Photodermatitis . . . . . . . . . . . . . .
3.2 Xerosis . . . . . . . . . . . . . . . . . . . .
3.3 Pruritus Associated with Systemic Illness
4. Conclusion . . . . . . . . . . . . . . . . . . . .

Abstract

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

.
.
.
.
.
.
.
.
.
.
.
.
.
.

177
178
180
180
181
182
182
183
184
185
185
185
186
186

With the advent of highly active antiretroviral therapy (HAART), life-threatening opportunistic infection
has become less common in patients with HIV infection and longevity has increased dramatically. With increased longevity, the problems of living with a chronic disease have become more prominent in this patient
population. Disorders such as fat redistribution and metabolic abnormalities can result from antiviral medications and from HIV disease itself. Pruritus is one of the most common symptoms encountered in patients with
HIV.
The spectrum of skin diseases in such patients encompasses dermatoses of diverse etiologies; a few are
peculiar to patients with HIV while others are not. Some of these conditions may cause severe and sometimes
intractable pruritus that provokes scratching, picking, disfigurement, sleep loss, and significant psychological
stress. Moreover, the expense of ongoing medical treatments can be daunting. Skin rash can sometimes be the
initial presentation of HIV infection or serve as a harbinger of disease progression.
Causes of pruritus include skin infections, infestations, papulosquamous disorders, photodermatitis, xerosis,
drug reactions, and occasionally lymphoproliferative disorders. Drug eruptions are particularly common in
patients who are HIV positive, presumably as a result of immune dysregulation, altered drug metabolism, and
polypharmacy. Itching can also result from systemic diseases such as chronic renal failure, liver disease, or
systemic lymphoma.
Workup of pruritus should include a careful examination of the skin, hair, nails, and mucous membranes to
establish a primary dermatologic diagnosis. If no dermatologic cause is found, a systemic cause or medicationrelated etiology should be sought. Idiopathic HIV pruritus is a diagnosis of exclusion and should only be
considered when a specific diagnosis cannot be established.
The management of HIV-associated pruritus should be directed at the underlying condition. Phototherapy
has been found to be useful in the treatment of several HIV-associated dermatoses and idiopathic pruritus as
well. Unfortunately, some of the treatments that have been suggested for patients with HIV are anecdotal or
based on small uncontrolled studies. The last decade has seen a surge in the utilization of HAART which, to
some degree, reconstitutes the immune system and ameliorates some dermatologic diseases. On the other hand,
some skin diseases flare temporarily when HAART is started. Unless frank drug allergy is suspected, HAART
does not need to be stopped.

178

The skin is probably the organ most commonly affected in

patients with HIV. With the introduction of highly active antiretroviral therapy (HAART), many patients are living longer[1]
and display chronic skin conditions that can be challenging to the
dermatologist. Among the conditions affecting the integument in
this population, some can cause severe and, at times, intractable
pruritus that provokes sleep loss, scratching, and picking that
sometimes leads to disfigurement and major psychological
stress.[2] The cost of physician visits, medications, and treatments, that may or may not be covered by health insurance plans,
not to mention time lost from work, causes added financial pressures to patients and their families. The range of skin diseases in
patients who are HIV-positive is broad, encompassing both HIV
and non-HIV related dermatoses. For example, skin rash can be
the initial presentation of HIV infection, or serve as the harbinger
of disease progression. The immune status of the patient, reflected in the CD4 T-cell count and viral load, is an important
parameter since there is often a strong correlation between the
CD4 count and the presence of particular HIV-associated rashes.
A number of skin diseases initiate a chronic itch-scratch-itch
cycle that can result in lichenification, excoriation, prurigo
nodularis, pigmentary alteration, and secondary infection.
Recent advances in the field of cutaneous neurobiology have
elucidated some mechanisms underlying pruritus but our understanding of these mechanisms is still in its infancy. It is thought
that both central and peripheral neurologic mediators may be involved. A number of chemical mediators including histamine,
serotonin, prostaglandins, cytokines, proteases, tachykinins (e.g.
substance P), and opioid peptides are thought to be involved on
a local level.[3]
The causes of pruritus in patients infected with HIV include
many ordinary dermatoses, some of which may be more severe
or more common in the setting of HIV infection. They include
papulosquamous disorders, infestations, infections, drug eruptions and occasionally lymphoproliferative disorders such as cutaneous T-cell lymphoma (CTCL). A variety of conditions peculiar to patients with HIV infection have been described. Atypical
cutaneous lymphoproliferative disorder (ACLD), also called
pseudo-Sezary or CTCL-simulant, presents as a pruritic, widespread eruption with pigmentary changes and an atypical lymphocytic infiltrate. This condition has been reported in patients
with late-stage HIV infection and rarely progresses to frank lymphoma.[4]
Drug eruptions are more common in patients with HIV infection than in their non-HIV-infected counterparts,[5] purportedly
as a result of immune dysregulation, altered drug metabolism,
and polypharmacy. They include morbilliform drug eruptions,
Stevens-Johnson syndrome, toxic epidermal necrolysis, drug hy Adis International Limited. All rights reserved.

Singh & Rudikoff

persensitivity syndrome, and photodermatitis related to sulfonamides, sulfones, and antiviral treatment. The protease inhibitor,
indinavir may cause a pruritic eruption.[6]
Some patients with HIV infection develop systemic diseases
that can cause pruritus. Among these are end-stage renal disease
from HIV nephropathy, chronic liver disease possibly from hepatitis B or C, or HAART-induced hepatotoxicity, hypothyroidism, and systemic lymphoma.[7-11] Evaluation should include
head-to-toe physical examination concentrating on the integument with laboratory testing dictated by the findings on history
and physical exam. In addition, the patients immune status
should be assessed by CD4 T-cell count and viral load. Optimum
anti-viral therapy should be instituted since it not only slows the
progression of HIV infection and increases life expectancy, but
also reportedly reverses certain HIV-related skin disorders.[12]
Some conditions such as eosinophilic folliculitis may be temporarily exacerbated on the initiation of HAART.[13,14]

1. Infections and Infestations

Infectious etiologies of pruritus such as scabies, pediculosis,
and folliculitis are encountered commonly in the HIV-infected
population but the incidence is not uniform in all risk groups.
Scabies may be more common in patients who acquired HIV via
sexual contact. A recent Japanese study showed a lower incidence
of certain infectious diseases such as molluscum contagiosum,
condyloma acuminata, and scabies in hemophiliac patients with
HIV, when compared with patients infected with HIV via methods other than blood transfusion.[15]
Several presentations of scabies, both usual and unusual,
have been reported in the setting of HIV infection. These include
typical interdigital burrows, nodular scabies, and crusted scabies
(see figure 1 and figure 2). Nodular scabies presents as erythematous nodules on the scrotum, penis, axillae, groin, and upper
back. It is a hypersensitivity reaction to mite proteins so usually
evident only in patients with intact cell-mediated immunity in
early HIV infection or after HAART treatment. Nodular scabies
may be confused with arthropod bites or with lymphomatoid
papulosis.
Patients with severe immune suppression may present with
overwhelming scabies mite infestations that may not be very pruritic because of absent cell-mediated inflammation. Patients with
scabies who are on HAART with attendant immune reconstitution can display significantly greater pruritus than patients with
crusted scabies. Itching may be worse at night.
Crusted scabies presents with localized or widespread hyperkeratotic plaques located on almost any part of the body. It can
occur in typical areas of scabetic involvement such as the web
Am J Clin Dermatol 2003; 4 (3)

HIV-Associated Pruritus

Fig. 1. Crusted scabies in a patient with HIV.

spaces of the hands, the genitals, and periaxillary region but also
in areas not usually involved such as the scalp and beard area.
The palms of the hands and soles of the feet may also be involved.
It can also present as generalized scaling. The presence of a dirty
grayish-brown scale in what appears to be a typical case of severe
xerosis, atopic dermatitis, or psoriasis suggests the diagnosis. It
is recommended that microscopic examination of skin scrapings
be performed to identify mites, eggs, or mite excreta. The presence of itching should be sought in household contacts as a diagnostic clue.
There are several important considerations in the treatment
of patients with scabies infestations. Since it is highly contagious
and may be spread via fomites, clothing and linens should be
carefully laundered in hot water. Another option is to isolate possibly infested garments in a closet for a few days before wearing
them. This is a reasonable course of action because mites can only
live a few days off the body. Family members should be offered
treatment to prevent ongoing reinfection in the household. Patients with crusted scabies shed considerable amounts of mitecontaining scales, which may contaminate the household environment. A recent study examining the households of patients
with scabies showed scabies mites in dust samples from 44% of
infested patients homes. Live mites were identified in 64% of
these homes, most often from bedroom floors or overstuffed
chairs and couches.[16]
The usual treatment of scabies infestation in non-pregnant,
adult patients includes the use of topical scabicides such as lindane lotion or 5% permethrin cream, applied for 812 hours from
the neck down before rinsing off. This is repeated a week later.
In patients with crusted scabies, more aggressive therapy is advocated. Topical keratolytics such as urea or lactic acid can be
Adis International Limited. All rights reserved.

179

applied to remove scale crust followed by more frequent use of

topical scabicides. Recurrences resulting from resistance to medication are uncommon. Inadequate treatment can result however,
because of the sheer number of mites and eggs, from failure to
apply sufficient scabicide, neglecting areas like the distal subungual nail beds, reinfection, or forgetting to treat fomites.
Oral ivermectin approved for the treatment of onchocerciasis, given once weekly at a dose of 200 g/kg bodyweight for a
total of two doses is an effective treatment for patients with
crusted scabies. Although not approved for the treatment of patients with scabies infestation, it has an excellent safety record.
In 19 patients without HIV who were treated for scabies with two
doses of ivermectin a week apart, there was a transient exacerbation of pruritus 2472 hours after the first dose of the study medication.[17] One study comparing one or two applications of
ivermectin with one overnight application of permethrin in the
treatment of patients with non-crusted scabies, found permethrin
to be superior to a single dose of ivermectin and equivalent to two
doses of ivermectin.[18] Although there are no published data
comparing the combination of ivermectin and permethrin with
either agent alone in the treatment of patients with crusted scabies, it may be advantageous to use the two agents together in
such patients. Ivermectin therapy should not be prescribed for
children under 33lb (15kg), and it should be prescribed only with
caution in women who are breast-feeding. Although it appears to
have a good safety profile in pregnancy, we do not treat scabies
in pregnant women with ivermectin.[19]
Antipruritic agents and topical corticosteroids may be helpful for relief of itching and antibacterials are indicated for the
treatment of secondarily infected lesions. Scabetic nodules require treatment with intralesional corticosteroid injections.

Fig. 2. Typical scabetic burrows in a patient with HIV.

Am J Clin Dermatol 2003; 4 (3)

180

Patients sometimes acquire pediculosis pubis (Phthirus) in

hair-bearing areas of the body, with itching as the dominant
symptom. The pubic area should be closely searched for nits, crab
lice, and maculae ceruleae (blue-gray spots where lice have fed).
The blue color is caused by the action of louse saliva on hemoglobin products. Pubic lice may also colonize other hairy areas
of the body, including the trunk in individuals with a lot of hair,
axillae, eyelashes, and occasionally the scalp. Treatment includes
agents such as permethrin, lindane lotion and malathion lotion.
Body louse infestation caused by pediculosis corporis is
much less common but should be considered in patients who are
homeless. In such cases, excoriations sometimes with secondary
infection, papular bite reactions, and post-inflammatory pigmentary changes are often observed. Lice sometimes can be found on
the body but, more commonly, are lurking in the seams of clothing.
Staphylococcus aureus is a frequent cause of cutaneous and
systemic bacterial infections in patients with HIV. S.aureus folliculitis is particularly common. It is characterized by widely
distributed pruritic, follicular pustules, and excoriated papules,
most commonly located on the arms and legs. Staphylococcal
impetigo may be seen in the axillae and groin. It presents as tender
erythematous erosions sometimes with satellite follicular pustules. Staphylococci may also exacerbate HIV-related atopic-like
dermatitis. Staphylococcal furuncles, abscesses, ecthyma, and
cellulitis are sometimes encountered in patients with HIV (figure
3). We have seen some patients with localized staphylococcal
infections presenting as ulcerations in the genital area that cleared
completely on systemic antibacterials.
A chronic recalcitrant toxic-shock-like disorder has been
described in patients infected with HIV.[20] These patients usually
present with widespread scaly, peeling erythroderma. S. aureus
can also superinfect molluscum contagiosum lesions and cause
them to feel itchy.
In some studies, such as that of Raviglione et al.,[21] higher
rates of staphylococcal nasal colonization were documented in
patients with HIV, suggesting a causative role in cutaneous staphylococcal infections. However, other investigators who examined the relationship between nasal carriage rates and disease
manifestations did not find a significant correlation.[22] Although
increased nasal carriage of staphylococci might be a source of
frequent staphylococcal skin infections, it might also reflect a
generalized susceptibility to staphylococcal colonization perhaps
as a result of alterations in adhesion molecules.
Treatment of staphylococcal infections includes oral antibacterials such as dicloxacillin, cefalexin, clindamycin or
ciprofloxacin, and topical treatment with antibacterial cleansers
such as chlorhexidine gluconate and topical antibacterial prepa Adis International Limited. All rights reserved.

Singh & Rudikoff

Fig. 3. Staphylococcal abscesses in a patient with HIV and leukopenia.

rations like mupirocin. Although, mupirocin ointment applied

intranasally in patients with HIV eradicated S. aureus for several
weeks, the effect waned over time with persistently negative cultures in 63, 45 and 29% of patients at 2, 6, and 10 weeks respectively.[23]

2. Non-Infectious Skin Diseases

2.1 Atopic-Like Dermatitis

Some patients with HIV infection develop a dermatitis that

strongly resembles atopic dermatitis and is sometimes referred to
as atopic-like dermatitis.[24,25] Although some of these patients
have a personal or family history of atopy such as asthma or
seasonal allergic rhinitis, the majority never experienced childhood eczema. There is often generalized xerosis and areas of
flexural or extensor lichenification on the arms, legs, and neck.
Extensive excoriation is usual and secondary infection and prurigo nodularis lesions are common. According to a recent survey
of individuals with HIV, up to 29% of those interviewed had
atopic manifestations, including chronic pruritic rashes or eczema.[26] Many of these patients had a personal or family history
of allergic rhinitis and asthma.
A hyperimmunoglobulinemia E (hyper-IgE)-like syndrome
has been described in patients with AIDS with hypereosinophilia,
hyper-IgE, chronic dermatitis and recurrent staphylococcal infections.[27] The immunologic mechanisms in this condition seem to
differ from those known in primary hyper-IgE syndrome, because
CD4+ T helper (Th) 2 type cells, which are currently believed to
have a role in IgE production, are severely depleted in patients
with AIDS.[28]
Am J Clin Dermatol 2003; 4 (3)

HIV-Associated Pruritus

It is currently thought that ordinary atopic dermatitis is initiated, in predisposed individuals, by a Th2-dominant (type-2)
cytokine milieu that goes on, in chronic lesions, to express the
Th1 cytokine, interferon-. There is some evidence that patients
with advanced HIV infection may develop a predominance of
type-2 cytokines and this is thought by some to predispose to
atopic manifestations. It has also been suggested that an allergen
specific IgE mechanism may contribute to eczematous reactions
in HIV-infected patients.[29]
Treatment of atopic-like dermatitis includes skin hydration,
avoidance of irritants, application of emollients, and the use of
topical corticosteroid preparations, preferably ointments. Since
these patients are frequently infected with staphylococci, oral
antibacterials may be indicated. We have also had success using
topical tacrolimus ointment to treat several patients and more
recently using pimecrolimus cream. The more challenging cases
are those with widespread lichenification or eczematous dermatitis. These will sometime require systemic corticosteroids for
flares. They should be started on phototherapy as soon as feasible
in order to limit systemic adverse effects or theoretical exacerbation of immunosuppression from long-term corticosteroid use.

2.2 Psoriasis

Patients with HIV can present with psoriasis that may sometimes be pruritic (figure 4). It is controversial whether the incidence of psoriasis is greater in patients with HIV but the incidence of psoriatic arthritis is definitely increased.[30] Psoriasis in
patients with HIV is frequently more extensive, destructive, and
therapy-resistant than its counterpart in immunocompetent patients. There is often a more acral distribution; psoriatic arthritis,
and destructive nail changes may be prominent.
In patients with known risk for HIV exposure, new onset
psoriasis may sometimes be a marker of HIV infection.[31] Erythroderma may occur in patients with HIV as a result of psoriasis,
atopic dermatitis, crusted scabies, and drug eruption. Erythroderma may be a presenting sign of HIV disease, especially in
young, Black patients.[32]
In a recent review, researchers studying psoriasis in patients
with HIV suggested that HIV-associated immune dysregulation
might trigger psoriasis in those carrying the HLA-Cw0602 allele.[33] In this schema, the HLA-Cw0602 allele might be a target
for CD8 cytotoxic T-lymphocytes (CTLs) responding to processed peptides presented in the context of major histocompatibility complex-1.
Treatment of patients with HIV-related psoriasis includes
HAART treatment, bland emollients, topical agents, phototherapy, and systemic antipsoriatic drugs. Antiviral therapy should
Adis International Limited. All rights reserved.

181

be optimized since clinical improvement of the skin often parallels reduction in HIV viral load induced by HAART.[34-37] As in
patients without HIV, emollients, salicylic acid preparations, tar,
topical corticosteroids, topical tazarotene, and topical calcipotriol are often useful for localized disease.
Phototherapy in the form of broadband ultraviolet (UV) B,
combined UVA/UVB or psoralen plus UVA (PUVA) is effective
for more extensive disease. Despite in vitro and transgenic mice
studies that suggest that UV light might cause progression of HIV
disease,[38,39] this has not borne out in clinical studies and UV
therapy is considered have a good safety profile by most investigators.[40] Gelfand et al.[40] found no increase in HIV viral load
in patients treated with UVB phototherapy. Moreover, pilot studies have not found evidence of increased HIV replication or activity in patients treated with PUVA.[41,42] Akaraphanth and
Lim[43] reviewed the published studies on UV-induced immunosuppression in patients with HIV and concluded that phototherapy and photochemotherapy appears to be safe in this patient
population.
It has been suggested that PUVA may be preferable to UVB
therapy in patients with thick plaques and palmoplantar involvement.[44] Since PUVA has recently been linked to a small increase
in the incidence of malignant melanoma in immunocompetent
patients, and since patient life span has been extended with the
advent of HAART, PUVA therapy should be used with care in
this patient population.[45]
Systemic retinoids such as acitretin or etretinate have proven
to be particularly useful for treatment of extensive psoriasis in
patients infected with HIV;[46] however, etretinate is no longer
being manufactured. Early case reports suggested that methotrex-

Fig. 4. Severe psoriasis in a patient with HIV.

Am J Clin Dermatol 2003; 4 (3)

182

Singh & Rudikoff

ate should not be used for HIV-related psoriasis because of leukopenia and death in some patients.[31] In a more recent report
there was no clear deterioration associated with methotrexate use
for AIDS-associated psoriatic arthritis.[47] Be that as it may,
methotrexate should only be used with careful monitoring. Practitioners should be particularly mindful of the fact that combined
use of methotrexate and trimethoprim/sulfamethoxazole (cotrimoxazole) can induce pancytopenia since many patients with
HIV take the latter drug for Pneumocystis carinii pneumonia prophylaxis.[48,49] Hydroxyurea (hydroxycarbamide) is a chemotherapeutic agent that has recently been looked at for possible antiviral effects in patients with HIV infection. Although this agent
has been used for treatment of severe psoriasis in immunocompetent patients, recent reports of hepatotoxicity cast doubt as to
whether this agent should be tried in patients with HIV-related
psoriasis.[50,51] Etanercept, a recombinant tumor necrosis factor receptor-Fc fusion protein can be quite effective for psoriatic
arthritis and psoriasis patients with HIV.[52] Some patients have
developed polymicrobial infections, so it should be used with
caution.

2.3 Seborrheic Dermatitis

Seborrheic dermatitis is a common dermatologic manifestation of HIV infection.[53] There is usually erythema, as well as
greasy scaling involving the nasolabial area, eyebrows, external
ears, postauricular areas and scalp. It can be more widespread and
recalcitrant to treatment in HIV-infected patients, however, with
involvement of most of the face including the forehead and malar
areas as well as other areas of the body such as the mid-chest,
axillae, groin, and back.
Seborrheic dermatitis often occurs early on in HIV-infection
(CD4 counts >500), or may reflect disease progression.[54-56] In
a recent longitudinal study of women with HIV, CD4 T-cell depletion and increased viral load were correlated with seborrheic
dermatitis and other skin abnormalities.[57] Although possible
overgrowth of the yeast Pityrosporum ovale has been suggested
as a cause for seborrheic dermatitis in patients with HIV, studies
have not borne this out.[58,59] The possible role of Pityrosporum
has recently been reviewed.[60] Occasionally, tinea faciei may be
confused with seborrheic dermatitis in patients with HIV.[61]
Patients with seborrheic dermatitis are usually treated with
low potency topical corticosteroids alone or in combination with
topical azole antifungals. Topical agents such as ketoconazole
and bifonazole are thought to have mild anti-inflammatory activity and are used to reduce the amount of corticosteroid needed.
Adjunctive therapy includes coal tar, selenium sulfide, and
pyrithione zinc and for severe disease narrow-band UVB photo Adis International Limited. All rights reserved.

therapy has been reported to be effective.[62] We have recently

found both tacrolimus ointment and pimecrolimus cream to be
efficacious in the treatment of patients with seborrheic dermatitis
(unpublished observation).

2.4 Pruritic Papular Eruptions

From early on in the HIV pandemic, patients with itchy papular eruptions have been described by a number of authors under
the moniker of papular eruption or pruritic papular eruption.[63]
James et al.[64] described a chronic waxing and waning, variably
pruritic eruption of noncoalescing, skin-colored papules of the
head, neck, and upper trunk measuring 2-5mm in seven patients
infected with HIV. A chronic perivascular mononuclear cell infiltrate was characteristic and eosinophils were sometimes present. One patient had granuloma formation.
Colebunders et al.[65] described a symmetrically distributed
papular eruption in African patients with AIDS that involved the
extensor surfaces of the arm, dorsa of the hands, lower legs, ankles, and dorsa of the feet. The lesions started as itchy papules
that released a clear fluid when scratched. On healing, they left
hyperpigmented macules.
Liautaud et al.[66] described a pruritic macular, papular, and
nodular eruption that started on the arms and later extended to the
legs, face (primarily the forehead) and trunk in a group of Haitian
patients. A mixed perivascular or perifollicular polymorphonuclear leukocyte infiltrate displayed a predominance of eosinophils. Of particular interest is that this eruption was not seen in
Haitian patients with AIDS who were living in New York City,
but was common in such patients in Miami, Florida, and Haiti as
well as in cases of patients reported from Zaire, Africa. The authors also stated categorically that the eruption was distinct from
eosinophilic pustular folliculitis and suggested it might represent
a reaction to insect saliva similar to papular urticaria.[67]
Hevia et al.[68] also described the histopathologic features of
pruritic papular eruption. A superficial and mid-dermal perivascular and perifollicular mononuclear cell infiltrate was associated with numerous eosinophils and varying follicular damage.
Eosinophilic folliculitis was found in 25% of patients. The authors considered that eosinophilic folliculitis as described in HIV
infection was part of the spectrum of pruritic papular eruption
and they also differentiated pruritic papular eruption from the
eruption described by James and colleagues.[64]
Eosinophilic folliculitis with histology reminiscent of
Ofujis disease has also been described in patients with HIV in a
number of reports.[69-72] It was predominantly localized on the
face, neck, upper chest, and back and upper arms. McCalmont et
al.[73] reviewed the histology of eosinophilic folliculitis and conAm J Clin Dermatol 2003; 4 (3)

HIV-Associated Pruritus

sidered it to be distinct from other papular eruptions. In a review

of the subject, Bason et al.[63] concluded that it is likely that pruritic papular eruption represents a spectrum of diseases, including
eosinophilic folliculitis. This interpretation agrees with the experience of the authors. Eosinophilic folliculitis, involving the face,
scalp, neck, upper chest and back and proximal arms appears
distinct from pruritic papular eruptions occurring predominantly
on the arms, legs and trunk although it is sometimes more widespread.
Whether these eruptions are one pathologic entity or distinct
will influence our interpretation of studies looking at histopathology and etiology. Ramos,[74] describing pruritic papular eruption
occurring predominantly on the extremities, noted a superficial
and deep perivascular lymphohistiocytic infiltrate with a variable
number of eosinophils. The density of dermal CD8+ lymphocytes
was increased while that of CD4+ lymphocytes was markedly
reduced. Rosatelli et al.,[75] not differentiating between pruritic
papular eruption and eosinophilic folliculitis, described the cutaneous infiltrate of pruritic papular eruption in a recent series.
They also found a predominance of CD8+ cells as well as a predominance of lymphocytes followed by mast cells and eosinophils in lesional skin but did not describe the histologic localization of the infiltrate (i.e. perivascular, folliculocentric, or both).
They concluded that the eruption was better described as pruritic
papular eruption than as eosinophilic folliculitis. This same group
also identified immediate cutaneous hypersensitivity to insect
antigens in patients with pruritic papular eruption.[76]
Most of our patients with pruritic papular eruption who do
not have typical eosinophilic folliculitis usually display histopathology somewhat reminiscent of papular urticaria that is not
folliculocentric (Phelps R, personal communication). If follicular
involvement is present, it is usually not the primary pathology as
seen in patients with eosinophilic folliculitis. It has been our opinion that this eruption is the result of a disordered immune response most likely to arthropod antigens or less likely to some as
yet not identified antigen. The process appears to be akin to papular urticaria. We consider eosinophilic folliculitis more likely to
be a reaction to some antigen in the pilosebaceous apparatus.
Other itchy papular eruptions occurring in patients with HIV,
besides eosinophilic (pustular) folliculitis and pruritic papular
eruption include prurigo nodularis, papular mucinosis and possibly some drug eruptions. The morphology and distribution of
these eruptions can be helpful in differentiating them. Lesions
may be pustular, urticarial, papular or polymorphic and folliculocentric or non-folliculocentric.
Whether there is actually a distinct clinical entity pruritic
papular eruption or whether it possibly represents a variant of
papular urticaria remains an open question in our opinion. As
Adis International Limited. All rights reserved.

183

mentioned previously in this section, we and others[63] regard it

as distinct from HIV-related eosinophilic folliculitis. We usually
reserve the diagnosis of pruritic papular eruption for eruptions
localized to the trunk and extremities that do not conform to more
well-defined entities such as eosinophilic folliculitis, arthropod
bites, scabies, and prurigo nodularis or drug reaction. Lesions are
usually excoriated and typically found on the extremities and
trunk with sparing of the palms, soles, and digital web spaces.
Pruritic papular eruption follows a chronic waxing and waning
course and may have an associated peripheral eosinophilia and
elevated levels of IgE.
Pruritic papular eruption is usually associated with advanced
HIV infection and severe immunosuppression. In one study,
81.25% and 75% of patients with pruritic papular eruption had
CD4 counts <100/mm3 and <50/mm3, respectively.[77] In a Haitian study, pruritic papular eruption was seen in 46% of patients
with AIDS and was the presenting manifestation in 79% of patients, often appearing months before the diagnosis of an AIDS
defining condition.[66] We have seen pruritic papular eruption as
the presenting sign of HIV infection but these patients usually
had very low CD4 counts to begin with.
Recent studies have looked at serum cytokine levels and
plasma kallikrein activity in pruritic papular eruption.[78,79]
Changes in serum interleukin-2 and interferon- and undetectable
plasma kallikrein activity were noted in patients with pruritic
papular eruption.
Pruritic papular eruption should be considered a marker for
severe immunosuppression. It may be difficult to treat with minimal response to antihistamines, topical antipruritic preparations,
and topical corticosteroids. UVB phototherapy is generally effective and is our treatment of choice. Ultra-potent topical corticosteroid ointments may provide some relief.

2.5 Eosinophilic Folliculitis

HIV-associated eosinophilic folliculitis was described in

1986.[69] At that time there was some confusion as to whether it
represented the same clinical entity as Ofujis disease because of
the similar pathology; however, there were significant differences in presentation.[72] In Ofujis disease there are pruritic circinate studded with follicular papules and sterile pustules on the
face, trunk, and arms.[80] The palms of the hands and soles of the
feet may occasionally be involved. Peripheral leukocytosis, eosinophilia, and elevated IgE levels are noted. Histologic exam
shows follicular spongiosis and folliculocentric mixed inflammatory infiltrate of eosinophils, lymphocytes, histiocytes, mast
cells, and neutrophils around the outer root sheaths of hair follicles.
Am J Clin Dermatol 2003; 4 (3)

184

In the variety of eosinophilic folliculitis associated with

HIV, patients present with discrete erythematous papules, or
papules surmounted by a tiny pustule, that involve the face, neck,
upper chest, upper back, and outer, proximal aspect of the arms
(figure 5). There may be eyelid involvement, post-auricular involvement and scalp lesions. In some patients, the eruption may
be more extensive involving the arms, legs and much of the torso.
Eosinophilic folliculitis is usually seen at CD4 T-cell counts
below 300/mm3.[72] Elevated IgE levels and peripheral eosinophilia have suggested that a type 2 cytokine response to an unknown antigen may cause eosinophilic folliculitis. Not only has
a type 2 cytokine response been described in late stage HIV infection but also recently investigators have shown increased expression of the type 2 cytokines, interleukin-4 and interleukin-5
and the chemokines RANTES and eotaxin in lesional skin of
patients with HIV-associated eosinophilic folliculitis. It has been
suggested that the disorder might be a result of immune dysregulation to a variety of agents such as Pityrosporum ovale, or
the follicular mite Demodex folliculorum, an autoimmune reaction to the sebocyte, or a component of sebum.[81]

Singh & Rudikoff

In a recent paper, Magro et al.[82] described a new entity

called necrotizing eosinophilic folliculitis, a novel manifestation
of the atopic diathesis. They described a small series of patients
with HIV who were atopic and developed an unconventional
form of eosinophilic folliculitis, characterized by ulceration, nodules, and dermal and follicular necrosis. They proposed that the
mechanism of this disease was an unrepressed Th2 type response
to epicutaneous stimuli in atopic individuals.
The typical clinical presentation of eosinophilic folliculitis
suggests the diagnosis, which is confirmed by biopsy or by the
demonstration of eosinophils on a Wrights stained smear from
an intact pustule. A recent study suggests that horizontal sectioning may be useful in diagnosing eosinophilic folliculitis.[83] Some
investigators have noted a decrease in eosinophilic folliculitis
prevalence with the advent of aggressive antiretroviral treatment,
although the immune reconstitution attendant with such treatment
can sometimes cause a flare up of eosinophilic folliculitis.[13,14]
Treatment options include phototherapy (UVB), oral metronidazole, itraconazole, and oral 13-cis-retinoic acid along with
antipruritic agents for symptomatic relief.[71,84-87]

2.6 Prurigo Nodularis

Fig. 5. Eosinophilic folliculitis in a patient with HIV.

Adis International Limited. All rights reserved.

Prurigo nodularis (pickers nodule) is a disorder characterized by hyperpigmented, excoriated, papules, nodules, and
plaques in patients with severe itching from a variety of causes.
In patients with HIV, it typically involves the arms, thighs, and
legs but it may be more extensive, sparing only areas that the
patient cannot reach. Pigmentary changes, more common in
darker skinned individuals include hyperpigmentation or central
hypopigmentation surrounded by hyperpigmentation. Ulceration
can be seen from uncontrolled picking (figure 6).
Causes of prurigo include itching from HIV-related dermatoses such as pruritic papular eruption, eosinophilic folliculitis
and papular urticaria, chronic renal failure, atopic dermatitis, and
cocaine addiction. Sometimes, the original cause of itching may
no longer be apparent.
The pathophysiology of prurigo nodularis is unclear. A striking feature of this disorder is the incessant, irrepressible scratching and picking seen in these patients. Whether primary immunologic or neurological mechanisms are paramount is not clear.
In patients infected with HIV, prurigo can follow papular urticaria induced by arthropod bites. Arthropod bites, in this population, are thought to cause an exaggerated, localized immune
response, intractable pruritus and subsequent formation of nodules. Penneys et al.[67] identified antibodies to mosquito salivary
gland antigens in patients with papular eruptions. They suggested
that in patients infected with HIV, non-specific B-cell activation
Am J Clin Dermatol 2003; 4 (3)

HIV-Associated Pruritus

Fig. 6. Ulcerated prurigo nodules in a patient with AIDS.

causes the formation of antibodies that react with these antigens

in the skin in a recall reaction.
It has also been suggested, based on polymerase chain reaction detection of mycobacterial DNA in lesional skin, that mycobacterial infection may be responsible for prurigo nodularis. It is
more likely that mycobacteria are implanted in these lesions by
chronic picking and scratching.[88]
There is evidence that neurologic or neuro-immune mechanisms are of importance. An increased number of histaminecontaining mast cells and increased number of nerve growth factor receptor (NGFr)-immunoreactive nerve fibers are found in the
upper dermis of prurigo nodularis lesional skin.[89] Mast cells are
seen in close vicinity to NGFr-positive nerves and sometimes
appeared to contact single nerve fibers.
The neuromediator, substance P, has also been implicated in
the pathophysiology of prurigo nodularis and topical capsaicin
has been used to treat this condition.[90,91]
Prurigo nodularis is typically resistant to treatment and a
frustrating challenge for practitioners. Topical super-potent corticosteroids under occlusion, intralesional corticosteroid injections, and phototherapy are the mainstays of treatment. Systemic
therapy with thalidomide appears to be a promising, effective
treatment for prurigo nodularis.[92] Thalidomide has both immunomodulatory and neurologic effects. Its mechanism of action
in prurigo remains to be determined.

185

porphyria cutanea tarda, or possibly an idiopathic photosensitivity brought on by advanced HIV disease. Berger and Dhar[93]
described pruritic, lichenoid photoeruptions in patients with HIV
and severe immunosuppression. The lichenoid lesions involved
the dorsa of the hands, forearms, face, and neck. The eruption
was most common in African-American patients and pigmentary
alterations both hyper- and hypopigmentation were seen (figure 7).
Photosensitivity in individuals infected with HIV appears to
be a manifestation of advanced disease. In one study, most patients were sensitive to UVB and more severely affected individuals were sensitive to both UVB and UVA, and sometimes visible
light.[94] Over one half of the patients had significant Native
American ancestry, an interesting finding since a polymorphous
light eruption of the American Indian has been described. In addition, subclinical photosensitivity was detected in patients with
eosinophilic folliculitis.
Treatment of photosensitivity eruptions includes avoidance
of sun exposure, use of topical sunblocks that block UVA and
UVB, and occasionally photochemotherapy (psoralen plus UVA
or PUVA) or oral retinoids. Thalidomide has also been reported
to be useful.[92]
3.2 Xerosis

Xerosis or dryness of the skin is one of the most common

findings in patients with HIV infection. Severe xerosis is seen in
about 20% of patients with HIV.[95] Xerosis is often prominent
on the extremities and worse in the winter months. It is frequently
accompanied by pruritus, excoriation, breaks in the skin, and secondary infection.

3. Miscellaneous Causes of Pruritus

3.1 Photodermatitis

Patients with HIV infection may develop photosensitivity

reactions from several causes including photosensitizing drugs,
Adis International Limited. All rights reserved.

Fig. 7. Lichenoid photodermatitis in a patient with HIV.

Am J Clin Dermatol 2003; 4 (3)

186

Singh & Rudikoff

Why patients with HIV develop xerosis is unclear, but some

have speculated that possible causes might include cutaneous
microcirculatory changes, changes in nutrient supply to the skin,
alteration of sweat or sebaceous gland activity, and changes in
mast cell population of the skin, all of which might effect the
epidermal barrier.[96] A search of Medline failed to reveal any
studies of epidermal lipids or natural moisturizing factor in HIVassociated xerosis. Rowe et al.[96] recently reported decreased
calcitonin gene related peptide (CGRP) and substance P levels in
the skin of patients with HIV-related xerosis. The authors postulated that decreased levels of CGRP and substance P may be
responsible for altered nutrition and blood supply in the epidermis leading to xerosis.
Treatment of xerosis includes skin hydration followed by
measures to maintain skin moisture. Soaking in a tub in tepid to
lukewarm water achieves hydration but unless an emollient is
applied soon after, evaporation will result in further drying and
chapping of the skin. Products such as petrolatum, Aquaphor1,
Eucerin cream, and lactic acid products such as Lactinol E
cream, Lachydrin cream or Amlactin, among many others,
should be applied to damp skin within 3 minutes after the patients shower or bath. Ointments such as petrolatum are preferable to creams or lotions but may not be tolerated by some patients. Soap application should be limited to intertriginous areas.
Mild, oilated soaps or soap substitutes are preferred. Cotton
clothing is preferable to wool, which can induce itching. Since
detergents can be irritating, it is helpful to add an extra rinse cycle
when washing clothing.

4. Conclusion
Pruritus is an important cause of discomfort and morbidity
in patients infected with HIV. Diagnosis involves a careful skin
examination to rule out a primary dermatologic etiology before
attributing itching to idiopathic HIV pruritus. The spectrum of
disease in the patient with HIV includes common dermatoses and
skin diseases peculiar to the immunosuppression and immune
dysregulation associated with HIV. An etiologic delineation of
HIV-associated pruritic diseases has been attempted in light of
recent advances in this field. If no dermatologic cause is found,
a systemic cause or medication-related etiology should be sought.

Acknowledgements
This manuscript was prepared by the authors with no outside funding.
Neither author has any conflict of interest relevant to the contents of this
manuscript.

References
1.
2.
3.
4.
5.

6.
7.

3.3 Pruritus Associated with Systemic Illness

8.

Pruritus in patients with HIV is usually caused by skin disease but less commonly, certain systemic diseases are identified
as the cause of itching. Chronic renal failure as a result of HIV
nephropathy, hepatic failure in patients with hepatitis (B or C),
or systemic lymphoma are sometimes implicated. Idiopathic HIV
pruritus, analogous to the pruritus of Hodgkins disease, is probably not very common and is diagnosed by exclusion of other
causes. Most patients will turn out to have mild xerosis or some
other identifiable cause of itching. Workup should include a complete history and physical exam, complete blood count with differential, liver and kidney function tests, hepatitis serologies, and
chest X-ray. Dermatographism occasionally causes pruritus in
HIV-infected patients. Medication induced pruritus should also
be considered.

9.

1 Use of tradenames is for product identification only and does not imply
endorsement.

17.

Adis International Limited. All rights reserved.

10.
11.

12.

13.
14.
15.
16.

Wong T, Chiasson MA, Reggy A, et al. Antiretroviral therapy and declining AIDS
mortality in New York City. J Urban Health 2000; 77: 492-500
Gelfand JM, Rudikoff D. Evaluation and treatment of itching in HIV-infected
patients. Mt Sinai J Med 2001; 68: 298-308
Greaves MW, Wall PD. Pathophysiology of itching. Lancet 1996; 348: 938-40
Friedler S, Parisi MT, Waldo E, et al. Atypical cutaneous lymphoproliferative
disorder in patients with HIV infection. Int J Dermatol 1999; 38: 111-8
Smith RJ, Skelton HG, Yeager J, et al. Increased drug reactions in HIV-1-positive
patients: a possible explanation based on patterns of immune dysregulation
seen in HIV-1 disease. Clin Exp Dermatol 1997; 22: 118-23
Gajewski LK, Grimone AJ, Melbourne KM, et al. Characterization of rash with
indinavir in a national patient cohort. Ann Pharmacother 1999; 33: 17-21
Szczech LA. Renal diseases associated with human immunodeficiency virus infection: epidemiology, clinical course, and management. Clin Infect Dis 2001;
33: 115-9
Bonacini M. Pruritus in patients with chronic human immunodeficiency virus,
hepatitis B and C virus infections. Dig Liver Dis 2000; 32: 621-5
Prakash M, Poreddy V, Tiyyagura L, et al. Jaundice and hepatocellular damage
associated with nevirapine therapy. Am J Gastroenterol 2001; 96: 1571-4
Lambert M. Thyroid dysfunction in HIV infection. Baillieres Clin Endocrinol
Metab 1994; 8: 825-35
Gabarre J, Raphael M, Lepage E, et al. Human immunodeficiency virus-related
lymphoma: relation between clinical features and histologic subtypes. Am J
Med 2001; 111: 704-11
Palella Jr FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality
among patients with advanced human immunodeficiency virus infection. HIV
Outpatient Study Investigators. N Engl J Med 1998; 338: 853-60
Handa S, Bingham JS. Dermatological immune restoration syndrome: does it
exist? J Eur Acad Dermatol Venereol 2001; 15: 430-2
Bachmeyer C, Cordier F, Cazier A, et al. Eosinophilic folliculitis associated with
AIDS after antiretroviral tri-therapy. Presse Med 1999; 28: 2226
Shimizu S, Chen KR, Tagami H, et al. Mucocutaneous manifestations in Japanese
HIV-positive hemophiliacs. Dermatology 2000; 201: 321-5
Arlian LG, Estes SA, Vyszenski-Moher DL. Prevalence of Sarcoptes scabiei in
the homes and nursing homes of scabietic patients. J Am Acad Dermatol 1988;
19: 806-11
Dourmishev A, Serafimova D, Dourmishev L. Efficacy and tolerance of oral
ivermectin in scabies. J Eur Acad Dermatol Venereol 1998; 11: 247-51

Am J Clin Dermatol 2003; 4 (3)

HIV-Associated Pruritus

18. Usha V, Gopalakrishnan Nair TV. A comparative study of oral ivermectin and
topical permethrin cream in the treatment of scabies. J Am Acad Dermatol 2000;
42: 236-40
19. Burkhart CN, Burkhart CG. Ivermectin: a few caveats are warranted before initiating therapy for scabies. Arch Dermatol 1999; 135: 1549-50
20. Cone LA, Woodard DR, Byrd RG, et al. A recalcitrant, erythematous, desquamating disorder associated with toxin-producing staphylococci in patients with
AIDS. J Infect Dis 1992; 165: 638-43
21. Raviglione MC, Mariuz P, Pablos-Mendez A, et al. High Staphylococcus aureus
nasal carriage rate in patients with acquired immunodeficiency syndrome or
AIDS-related complex. Am J Infect Control 1990; 18: 64-9
22. Holbrook KA, Klein RS, Hartel D, et al. Staphylococcus aureus nasal colonization
in HIV-seropositive and HIV-seronegative drug users. J Acquir Immune Defic
Syndr Hum Retrovirol 1997; 16: 301-6
23. Martin JN, Perdreau-Remington F, Kartalija M, et al. A randomized clinical trial
of mupirocin in the eradication of Staphylococcus aureus nasal carriage in human immunodeficiency virus disease. J Infect Dis 1999; 180: 896-9
24. Cockerell CJ. Seborrheic dermatitis-like and atopic dermatitis-like eruptions in
HIV-infected patients. Clin Dermatol 1991; 9: 49-51
25. Rudikoff D. The relationship between HIV infection and atopic dermatitis. Curr
Allergy Asthma Rep 2002; 2: 275-81
26. Lin RY, Lazarus TS. Asthma and related atopic disorders in outpatients attending
an urban HIV clinic. Ann Allergy Asthma Immunol 1995; 74: 510-5
27. Lin RY. Chronic diffuse dermatitis and hyper-IgE in HIV infection. Acta Derm
Venereol 1988; 68: 486-91
28. Paganelli R, Scala E, Mezzaroma I, et al. Immunologic aspects of hyperimmunoglobulinemia E-like syndrome in patients with AIDS. J Allergy Clin
Immunol 1995; 95: 995-1003
29. Nissen D, Nolte H, Permin H, et al. Evaluation of IgE-sensitization to fungi in
HIV-positive patients with eczematous skin reactions. Ann Allergy Asthma
Immunol 1999; 83: 153-9
30. Solinger AM, Hess EV. Rheumatic diseases and AIDS: is the association real? J
Rheumatol 1993; 20: 678-83
31. Duvic M, Johnson TM, Rapini RP, et al. Acquired immunodeficiency syndromeassociated psoriasis and Reiters syndrome. Arch Dermatol 1987; 123: 1622-32
32. Morar N, Dlova N, Gupta AK, et al. Erythroderma: a comparison between HIV
positive and negative patients. Int J Dermatol 1999; 38: 895-900
33. Mallon E, Young D, Bunce M, et al. HLA-Cw*0602 and HIV-associated psoriasis.
Br J Dermatol 1998; 139: 527-33
34. Fischer T, Schworer H, Vente C, et al. Clinical improvement of HIV-associated
psoriasis parallels a reduction of HIV viral load induced by effective antiretroviral therapy. AIDS 1999; 13: 628-9
35. Duvic M, Crane MM, Conant M, et al. Zidovudine improves psoriasis in human
immunodeficiency virus-positive males. Arch Dermatol 1994; 130: 447-51
36. Kaplan MH, Sadick NS, Wieder J, et al. Antipsoriatic effects of zidovudine in
human immunodeficiency virus-associated psoriasis. J Am Acad Dermatol
1989; 20: 76-82
37. Ruzicka T, Froschl M, Hohenleutner U, et al. Treatment of HIV-induced retinoidresistant psoriasis with zidovudine. Lancet 1987; II: 1469-70
38. Akaraphanth R, Lim HW. HIV, UV and immunosuppression. Photdermatol Photoimmunol Photomed 1999; 15: 28-31
39. Morrey JD, Bourn SM, Bunch TD, et al. In vivo activation of human immunodeficiency virus type 1 long terminal repeat by UV type A (UV-A) light plus
psoralen and UV-B light in the skin of transgenic mice. J Virol 1991; 65: 5045-51
40. Gelfand JM, Rudikoff D, Lebwohl M, et al. Effect of UV-B phototherapy on plasma
HIV type 1 RNA viral level: a self-controlled prospective study. Arch Dermatol
1998; 134: 940-5
41. Ranki A, Puska P, Mattinen S, et al. Effect of PUVA on immunologic and virologic
findings in HIV-infected patients. J Am Acad Dermatol 1991; 24: 404-10
42. Pechere M, Yerly S, Lemonnier E, et al. Impact of PUVA therapy on HIV viremia:
a pilot study. Dermatology 1997; 195: 84-5

Adis International Limited. All rights reserved.

187

43. Akaraphanth R, Lim HW. HIV, UV and immunosuppression. Photodermatol Photoimmunol Photomed 1999; 15: 28-31
44. Morison WL. PUVA therapy is preferable to UVB phototherapy in the management
of HIV-associated dermatoses. Photochem Photobiol 1996; 64: 267-8
45. Stern RS, Nichols KT, Vakeva LH. Malignant melanoma in patients treated for
psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA): the
PUVA follow-up study. N Engl J Med 1997; 336: 1041-5
46. Buccheri L, Katchen BR, Karter AJ, et al. Acitretin therapy is effective for psoriasis
associated with human immunodeficiency virus infection. Arch Dermatol 1997;
133: 711-5
47. Maurer TA, Zackheim HS, Tuffanelli L, et al. The use of methotrexate for treatment
of psoriasis in patients with HIV infection. J Am Acad Dermatol 1994; 31: 372-5
48. Thomas DR, Dover JS, Camp RD. Pancytopenia induced by the interaction between methotrexate and trimethoprim-sulfamethoxazole. J Am Acad Dermatol
1987; 17: 1055-6
49. Groenendal H, Rampen FH. Methotrexate and trimethoprim-sulphamethoxazole:
a potentially hazardous combination. Clin Exp Dermatol 1990; 15: 358-60
50. Kumar B, Saraswat A, Kaur I. Rediscovering hydroxyurea: its role in recalcitrant
psoriasis. Int J Dermatol 2001; 40: 530-4
51. Reisler K. High hepatotoxicity rate seen among HAART patients. Aids Alert 2001;
16: 118-9
52. Aboulafia DM, Bundow D, Wilske K, et al. Etanercept for the treatment of human
immunodeficiency virus-associated psoriatic arthritis. Mayo Clin Proc 2000; 75:
1093-8
53. Matis WL, Triana A, Shapiro R, et al. Dermatologic findings associated with human immunodeficiency virus infection. J Am Acad Dermatol 1987; 17: 746-51
54. Berger RS, Stoner MF, Hobbs ER, et al. Cutaneous manifestations of early human
immunodeficiency virus exposure. J Am Acad Dermatol 1988; 19: 298-303
55. Mirowski GW, Hilton JF, Greenspan D, et al. Association of cutaneous and oral
diseases in HIV-infected men. Oral Dis 1998; 4: 16-21
56. Montella F, Pezzotti P, Di Sora F, et al. Improving the prognostic value of CD4+
count using IgA and clinical signs in HIV-seropositive IV drug users. Infection
1997; 25: 117-20
57. Mirmirani P, Hessol NA, Maurer TA, et al. Prevalence and predictors of skin
disease in the Womens Interagency HIV Study (WIHS). J Am Acad Dermatol
2001; 44: 785-8
58. Ross S, Richardson MD, Graybill JR. Association between Malassezia furfur colonization and seborrhoeic dermatitis in AIDS patients. Mycoses 1994; 37: 367-70
59. Wikler JR, Nieboer C, Willemze R. Quantitative skin cultures of Pityrosporum
yeasts in patients seropositive for the human immunodeficiency virus with and
without seborrheic dermatitis. J Am Acad Dermatol 1992; 27: 37-9
60. Bergbrant IM. Seborrhoeic dermatitis and Pityrosporum yeasts. Curr Top Med
Mycol 1995; 6: 95-112
61. Perniciaro C, Peters MS. Tinea faciale mimicking seborrheic dermatitis in a patient
with AIDS. N Engl J Med 1986; 314: 315-6
62. Pirkhammer D, Seeber A, Honigsmann H, et al. Narrow-band ultraviolet B (ATL01) phototherapy is an effective and safe treatment option for patients with
severe seborrhoeic dermatitis. Br J Dermatol 2000; 143: 964-8
63. Bason MM, Berger TG, Nesbitt Jr LT. Pruritic papular eruption of HIV-disease.
Int J Dermatol 1993; 32: 784-9
64. James WD, Redfield RR, Lupton GP, et al. A papular eruption associated with
human T cell lymphotropic virus type III disease. J Am Acad Dermatol 1985;
13: 563-6
65. Colebunders R, Mann JM, Francis H, et al. Generalized papular pruritic eruption
in African patients with human immunodeficiency virus infection. AIDS 1987;
1: 117-21
66. Liautaud B, Pape JW, DeHovitz JA, et al. Pruritic skin lesions: a common initial
presentation of acquired immunodeficiency syndrome. Arch Dermatol 1989;
125: 629-32
67. Penneys NS, Nayar JK, Bernstein H, et al. Chronic pruritic eruption in patients with
acquired immunodeficiency syndrome associated with increased antibody titers
to mosquito salivary gland antigens. J Am Acad Dermatol 1989; 21: 421-5

Am J Clin Dermatol 2003; 4 (3)

188

68.

69.

70.
71.

72.

73.
74.

75.

76.

77.

78.
79.
80.
81.

82.
83.

Singh & Rudikoff

Hevia O, Jimenez-Acosta F, Ceballos PI, et al. Pruritic papular eruption of the

acquired immunodeficiency syndrome: a clinicopathologic study. J Am Acad
Dermatol 1991; 24: 231-5
Soeprono FF, Schinella RA. Eosinophilic pustular folliculitis in patients with
acquired immunodeficiency syndrome: report of three cases. J Am Acad
Dermatol 1986; 14: 1020-2
Jenkins Jr D, Fisher BK, Chalvardjian A, et al. Eosinophilic pustular folliculitis
in a patient with AIDS. Int J Dermatol 1988; 27: 34-5
Buchness MR, Lim HW, Hatcher VA, et al. Eosinophilic pustular folliculitis in
the acquired immunodeficiency syndrome: treatment with ultraviolet B phototherapy. N Engl J Med 1988; 318: 1183-6
Rosenthal D, LeBoit PE, Klumpp L, et al. Human immunodeficiency virus-associated eosinophilic folliculitis: a unique dermatosis associated with advanced
human immunodeficiency virus infection. Arch Dermatol 1991; 127: 206-9
McCalmont TH, Altemus D, Maurer T, et al. Eosinophilic folliculitis: the histologic spectrum. Am J Dermatopathol 1995; 17: 439-46
Ramos H. Erupcao papular pruritica associada ao virus da imunodeficiencia humana: etiopatogenese avaliada por analise clinica, imunohistoquimica e ultraestructural. Rev Soc Bras Med Trop 1999; 32: 199-200
Rosatelli JB, Soares FA, Roselino AM. Pruritic papular eruption of the acquired
immunodeficiency syndrome: predominance of CD8+ cells. Int J Dermatol
2000; 39: 873-4
Rosatelli JB, Roselino AM. Hyper-IgE, eosinophilia, and immediate cutaneous
hypersensitivity to insect antigens in the pruritic papular eruption of human
immunodeficiency virus. Arch Dermatol 2001; 137: 672-3
Boonchai W, Laohasrisakul R, Manonukul J, et al. Pruritic papular eruption in
HIV seropositive patients: a cutaneous marker for immunosuppression. Int J
Dermatol 1999; 38: 348-50
Aires JM, Rosatelli JB, de Castro Figueiredo JF, et al. Cytokines in the pruritic
papular eruption of HIV. Int J Dermatol 2000; 39: 903-6
Reis ML, Maeda S, Rosatelli JB, et al. Kininogens and kallikrein in pruritic papular eruption. Immunopharmacology 1999; 45: 115-20
Colton AS, Schachner L, Kowalczyk AP. Eosinophilic pustular folliculitis. J Am
Acad Dermatol 1986; 14: 469-74
Fearfield LA, Rowe A, Francis N, et al. Itchy folliculitis and human immunodeficiency virus infection: clinicopathological and immunological features,
pathogenesis and treatment. Br J Dermatol 1999; 141: 3-11
Magro CM, Crowson AN. Necrotizing eosinophilic folliculitis as a manifestation
of the atopic diathesis. Int J Dermatol 2000; 39: 672-7
Piantanida EW, Turiansky GW, Kenner JR, et al. HIV-associated eosinophilic
folliculitis: diagnosis by transverse histologic sections. J Am Acad Dermatol
1998; 38: 124-6

Adis International Limited. All rights reserved.

84.

85.

86.

87.

88.
89.

90.

91.
92.
93.
94.
95.

96.

Smith KJ, Skelton HG, Yeager J, et al. Metronidazole for eosinophilic pustular
folliculitis in human immunodeficiency virus type 1-positive patients. Arch
Dermatol 1995; 131: 1089-91
Berger TG, Heon V, King C, et al. Itraconazole therapy for human immunodeficiency virus-associated eosinophilic folliculitis. Arch Dermatol 1995; 131:
358-60
Otley CC, Avram MR, Johnson RA. Isotretinoin treatment of human immunodeficiency virus-associated eosinophilic folliculitis: results of an open, pilot trial.
Arch Dermatol 1995; 131: 1047-50
Blauvelt A, Plott RT, Spooner K, et al. Eosinophilic folliculitis associated with
the acquired immunodeficiency syndrome responds well to permethrin. Arch
Dermatol 1995; 131: 360-1
Mattila JO, Vornanen M, Vaara J, et al. Mycobacteria in prurigo nodularis: the
cause or a consequence? J Am Acad Dermatol 1996; 34: 224-8
Liang Y, Marcusson JA, Jacobi HH, et al. Histamine-containing mast cells and
their relationship to NGFr-immunoreactive nerves in prurigo nodularis: a reappraisal. J Cutan Pathol 1998; 25: 189-98
Abadia Molina F, Burrows NP, Jones RR, et al. Increased sensory neuropeptides
in nodular prurigo: a quantitative immunohistochemical analysis. Br J
Dermatol 1992; 127: 344-51
Stander S, Luger T, Metze D. Treatment of prurigo nodularis with topical capsaicin. J Am Acad Dermatol 2001; 44: 471-8
Berger TG, Hoffman C, Thieberg MD. Prurigo nodularis and photosensitivity in
AIDS: treatment with thalidomide. J Am Acad Dermatol 1995; 33: 837-8
Berger TG, Dhar A. Lichenoid photoeruptions in human immunodeficiency virus
infection. Arch Dermatol 1994; 130: 609-13
Vin-Christian K, Epstein JH, Maurer TA, et al. Photosensitivity in HIV-infected
individuals. J Dermatol 2000; 27: 361-9
Coldiron BM, Bergstresser PR. Prevalence and clinical spectrum of skin disease
in patients infected with human immunodeficiency virus. Arch Dermatol 1989;
125: 357-61
Rowe A, Mallon E, Rosenberger P, et al. Depletion of cutaneous peptidergic
innervation in HIV-associated xerosis. J Invest Dermatol 1999; 112: 284-9

Correspondence and offprints: Dr Donald Rudikoff, Department of Dermatology, Mount Sinai Medical Center, 1 Gustave L. Levy Place, PO Box 1048,
New York, NY 10029, USA.
E-mail: RNAhybrid@aol.com

Am J Clin Dermatol 2003; 4 (3)