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CPJXXX10.1177/0009922816683501Clinical PediatricsArthur et al
Brief Report
Lymphomatoid Papulosis in a
2-Year-Old Girl With Markedly Elevated
Antinuclear Antibodies: A Case Report
Joshua Daniel Arthur, MD, MTS1, Andrew James Rand, MD2,
Kelly L. West, MD, PhD3,4, and Diana Borton McShane, MD5
Introduction
Lymphomatoid papulosis (LyP) is a rare papulonodular
skin disorder of unknown etiology characterized by
recurrence over years or decades. Included in the spec-
trum of CD30-positive T-cell lymphoproliferative disor-
ders in the 2008 World Health Organization classification
of hematopoietic and lymphoid tumors, LyP demon-
strates overlapping features with primary cutaneous
anaplastic large cell lymphoma, but usually follows a
more benign course.1-3 In this article, we report the case
of a 2-year-old girl presenting with persistent pruritic
papules and markedly elevated antinuclear antibodies
(ANA) whose overall clinical course was consistent
with LyP.
Case
A 2-year-old previously healthy girl presented to her
pediatrician at a military base in Sicily 6 days after the
abrupt onset of intensely pruritic, eroded, edematous
papules involving the torso, legs, arms, face, and scalp
(Figure 1A-C). She did not have a history of atopy or
recent illness. Over the ensuing 4 weeks, she was pre-
scribed oral antihistamines and moderate-potency topi-
cal steroids without any decrease in pruritus or the
prevalence of new lesions. A biopsy was performed and
oral prednisolone was initiated at 2 mg/kg/day for 5
days. The prednisolone resulted in some improvement
and was weaned over 4 weeks; however, new lesions
continued to emerge.
The initial biopsy demonstrated leukocytoclastic vas-
culitis with neutrophilic predominance but did not yield
a clear diagnosis. With the exception of a high titer posi-
tive ANA of 1:2560, initial screening labs were normal,
including a complete blood count, urinalysis, complete
metabolic panel, celiac panel, antineutrophil cytoplas-
mic antibody, C-reactive protein, and erythrocyte sedi-
mentation rate. Follow-up testing was normal for
lupus-specific antibodies, complement C3, complement
C4, and parvovirus B19, but the ANA remained elevated
Clinical Pediatrics
2017, Vol. 56(14) 1357­–1360
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at 1:5120, with homogenous and speckled patterns pres-
ent. Trials of DEET and permethrin were attempted
without effect. Oral erythromycin was initiated at 37
mg/kg/day due to the clinical impression of pityriasis
lichenoides et varioliformis acuta (PLEVA).
Due to the elevated ANA, absence of a clear diagno-
sis, complete return of the lesions after weaning from
oral steroids, and a lack of local pediatric subspecialists,
the patient was referred to a tertiary care center in the
United States. Despite the change in environment, she
continued to develop new crops of lesions greater than
10 weeks after the initial presentation. A pediatric rheu-
matology evaluation confirmed the prior lab results and
was negative for other signs of systemic disease.
At that point, the biopsy was repeated and demon-
strated a primarily folliculocentric infiltrate of lympho-
cytes and eosinophils with some involvement of the
superficial dermis (Figure 2A). There was not sufficient
interface dermatitis (basal vacuolar change and necrotic
keratinocytes) to support PLEVA. Lymphocytes were
generally small and mixed with rare larger, more atypi-
cal cells (Figure 2B). An immunohistochemical stain for
CD30 highlighted the large lymphocytes and revealed
no significant grouping (Figure 2C); an immunohisto-
chemical stain for CD8 highlighted many small lympho-
cytes. The histologic findings were nonspecific and
suggested a differential diagnosis that included pro-
cesses such as drug or viral reaction, folliculitis, insect
bites, or an unusual LyP. Due to the clinical findings of
recurrent crops of erythematous eroded papules that
1
Saint Louis University, St Louis, MO, USA
2
3
Medical University of South Carolina, Charleston, NC, USA
Ball Dermpath, Greensboro, NC, USA
4
Duke University, Durham, NC, USA
5
University of North Carolina at Chapel Hill, NC, USA
Corresponding Author:
Joshua Daniel Arthur, Department of Pediatrics, Saint Louis
University, 1465 South Grand Boulevard, St Louis, MO 63104-1095,
USA.
Email: arthurjd@slu.edu
1358 Clinical Pediatrics 56(14)

Figure 1.  Clinical photographs from the patient’s initial presentation: (A) Diffuse eroded papules were most pronounced on
the extremities. (B) Facial involvement was less severe than that of the extremities. (C) Additional lesions were noted on the
lower back.

Figure 2.  Photomicrographs from a 3-mm punch biopsy of a crusted papule on the right posterior leg: (A) A low-power view
demonstrates a primarily folliculocentric infiltrate of inflammatory cells with some involvement of the superficial dermis. (B) A
high-power view shows the perifollicular infiltrate of eosinophils and generally small lymphocytes with scattered larger, more
atypical cells. (C) An immunohistochemical stain for CD30 highlights scattered, large lymphocytes without significant grouping.

continued to emerge despite the patient’s change in
environment, the patient’s clinical course was deter-
mined to be most consistent with LyP and she was con-
tinued on oral erythromycin and fluocinonide 0.05%
ointment.
Over the next 3 months, the patient’s lesions slowly
resolved with residual mild hypopigmentation and scar-
ring on her arms and legs, supporting the diagnosis of
LyP. At that time, a repeat ANA of 1:20 480 was obtained
without development of any additional symptoms. A
new crop of eroded papules recurred 9 months later with
15 to 20 lesions on her face, arms, and stomach; how-
ever, these papules elicited only mild pruritis and lasted
for only a month. At the time of article submission,
approximately 2 years after the lesions first appeared,
there were neither further recurrences of the skin lesions
nor clinical evidence of rheumatologic disease.
Discussion
In general, LyP occurs in adults between the ages of 40
and 60,2 but up to 11% of cases may be in pediatric
patients, with a mean age at presentation of 7.5 to 12
years.3-6 Patients present with recurrent eruptions of less
than 2 cm grouped or disseminated reddish brown pap-
ules and nodules symmetrically distributed on the limbs,
trunk, or face that can be associated with pruritus in 40%
of cases. The lesions may increase in size or develop
central hemorrhage or necrosis prior to spontaneously
resolving weeks to months later, leaving residual
Arthur et al 1359
hypopigmentation, hyperpigmentation, or atrophic scars
in up to 83% of affected patients.3,6 Although many
patients will never experience more than 50 lesions at a
time,3,6 some patients will present with over 100 lesions.3
Outbreaks can last for weeks to months with disease-
free intervals of weeks to years; however, in one series,
15 of 35 patients never experienced complete remission
of the disease, with 40% experiencing continuous active
disease 10 years after onset.3 Systemic symptoms should
be absent; if present, such findings would raise the con-
cern for alternative diagnoses such as malignancy. In
addition to other lymphoproliferative diseases such as
mycosis fungoides and some pseudo-lymphomas,7 the
differential diagnosis for the lesions observed in LyP
includes PLEVA, insect bites, nodular scabies, lympho-
matoid drug eruption, impetigo, and viral infections
such as varicella or herpes simplex. Various series have
shown associations with pityriasis lichenoides,4 atopic
dermatitis, and antecedent viral infection.3,6,8
Our patient’s histology was not classic, possibly due
to her being on treatment at the time of biopsy, which
precluded histologic subtyping. However, traditionally
lesions may be thought of as falling into one of several
different categories, with occasional overlap. Type A,
the most common type, particularly in children,2,4,6,9 is
characterized by a mixed, wedge-shaped inflammatory
infiltrate with large atypical CD30-positive cells that are
similar to the Reed-Sternberg cells seen in Hodgkin
lymphoma.8,9 Type B exhibits an infiltrate of smaller
lymphocytes with a cerebriform nuclei that mimics
mycosis fungoides, thus requiring clinical correlation to
differentiate between the two. Type C is almost identical
to anaplastic large cell lymphoma, containing sheets of
large atypical lymphocytes with fewer inflammatory
cells.2-4,8 Recently described types D and E resemble
aggressive epidermotropic CD8+ T cell lymphoma10
and aggressive angioinvasive T cell lymphoma,11
respectively. Finally, and of particular interest to our
case, LyP may rarely demonstrate follicular involve-
ment; some authors have proposed describing these
lesions as type F.7 There is no clear prognostic differ-
ence between the various types, although a mixed histo-
logic type may confer an increased risk of malignancy.2
The significance of the elevated ANA in conjunction
with the patient’s skin disorder is unclear. While there
are case reports of patients with both low titer positive
ANA and LyP,12,13 high titer positive ANA in a patient
with LyP has not been reported. There are 2 series that
explore the relationship between other lymphoprolifera-
tive disorders and elevated ANA. While Peterson et al
showed no correlation between ANA seropositivity and
cutaneous T-cell lymphoma,14 Guyomard et al demon-
strated that elevated ANA was significantly associated
with non-Hodgkin’s lymphoma (NHL), describing an
elevated ANA in 19% of patients with NHL versus 5.6%
of control patients.15 Moreover, autoantibodies directed
against proteins involved in mitosis were found in 6.9%
of NHL patients versus 0.5% in the control group.
Proposed explanations for these findings included a role
for ANA in antitumor surveillance.15 In the case of our
patient, it is possible that the proliferation of atypical
lymphoid cells in LyP triggered a rise in ANA by similar
mechanisms.
Most reported complications of LyP have occurred in
adults, with 5% to 20% experiencing lymphoprolifera-
tive disease.8 The most common malignant complica-
tion is mycosis fungoides but anaplastic large cell
lymphoma and Hodgkin lymphoma have also been
reported.2,4 With less than 150 published cases of pediat-
ric LyP,6 it is difficult to quantify an absolute risk of
malignancy; however, in the largest series of children
with LyP, Nijsten et al described 3 cases of non-Hodgkin
lymphoma out of 35 children with LyP (9% of patients).
This is more than 200 times the expected incidence of
non-Hodgkin lymphoma in children and suggests a risk
of malignancy similar to that of adults with LyP (10%).3
Other studies reported 9 pediatric cases of anaplastic
large cell lymphoma in children with LyP and 2 late-
onset lymphomas that developed in adults who began
experiencing LyP as children.3,6 Thus, close follow-up
of patients with LyP is indicated, including regular skin
examinations and evaluations for lymph node, liver, or
splenic enlargement.6,9
While there is no standard therapy for children, vari-
ous treatments have been advocated for symptomatic
care, including topical corticosteroids, oral antibiotics
(macrolides or tetracyclines), ultraviolet B or natural
sunlight, PUVA, and low-dose methotrexate.6 None
seem to alter the ultimate course of LyP, since it is most
common for the lesions to regress spontaneously.2,8
In summary, this article describes an unusual case
best classified as LyP in one of the youngest patients to
date in the published literature.3,6 Overall, she has fol-
lowed an encouraging course, experiencing improve-
ment on topical steroids and oral erythromycin with
minimal scarring. Interestingly, she continued to dem-
onstrate a markedly elevated ANA without systemic
symptoms even after her cutaneous lesions resolved.
Acknowledgments
The authors thank M. Angelica Selim, MD, Director of the
Dermatopathology Unit at Duke University, for expert inter-
pretation of the patient’s second biopsy. Additionally they
thank Steven Conlon and Susan Reeves from PhotoPath in the
Department of Pathology at Duke University for skillful assis-
tance with microscopic photography and figure design.
1360 Clinical Pediatrics 56(14)
Author Contributions
JDA developed the manuscript concept and design and drafted
the manuscript. All of the authors contributed to the acquisi-
tion and interpretation of data, revised the manuscript criti-
cally for important intellectual content and approved the
version to be published.
Authors’ Note
Institutional board approval was not necessary for the writing
of this case report. Informed consent was obtained from the
patient’s parents for use of patient photographs.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
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