Pityriasis Lichenoides Clinical And Immunogenetic Studies
Medicina, Ribeirão Preto,
Simpósio ASSOCIAÇÃO DO SISTEMA HLA COM DOENÇAS NO BRASIL
33: 32-36, jan./mar. 2000
Capítulo IV
PITYRIASIS LICHENOIDES - CLINICAL AND
IMMUNOGENETIC STUDIES
PITIRÍASE LIQUENÓIDE - ESTUDOS CLÍNICOS E IMUNOGENÉTICOS
Norma T Foss1; Luiz S D’Oliveira Rocha2; Ana Maria F Roselino1 & Eduardo A Donadi3
1Docentes da Divisão de Dermatologia. 2Médico Assistente da Divisão de Moléstias Infecciosas. 3Docente da Divisão de Imunologia
Clínica. Departamento de Clínica Médica - Faculdade de Medicina de Ribeirão Preto-USP,
CORRESPONDENCE: Norma T. Foss, Division of Dermatology, Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto - USP
- 14049-900 Ribeirão Preto, SP, Brazil. Fax: 16 633 0236 - E-mail: ntfoss@fmrp. Usp.br
FOSS NT; ROCHA LSD; ROSELINO AMF & DONADI EA.
Pityriasis lichenoides - clinical and immunogenetic
studies. Medicina, Ribeirão Preto, 33: 32-36, jan./march 2000.
ABSTRACT: Type of study: Prevalence study.
Objectives: Despite pityriasis lichenoides is an uncommon dermatosis, we observed 12 cases
in the last 3 years. By this means, we review clinical and histopathologic findings of all patients
with pityriasis lichenoides seen at our Division. Furthermore, since pathogenic features of the
disease are unknown, we performed HLA class I and II typings to search for possible immunogenetic
markers for pityriasis lichenoides.
Methods: Twenty-one patients with biopsy-proven diagnosis of pityriasis lichenoides were
evaluated. HLA class I and II antigens were typed using conventional serological procedures.
Results: Children and young adults were predominantly affected. Most of the cases were seen
in fall and winter time. Typical disseminated lesions were observed more frequently. Both acute
and chronic patterns were observed at histology. Compared to controls, the HLA-B17 antigen was
overrepresented in patients (P < 0.005).
Conclusions: Although pityriasis lichenoides remains a cutaneous disease of undetermined
origin, our findings show that the disease is associated with the HLA-B17 antigen.
UNITERMS:
Pityriasis Lichenoides. HLA Antigens. Histology. Immunogenetics.
1. INTRODUCTION
beneficial, etiopathogenic mechanisms have not been
elucidated. Immune complexes, cell-mediated
Pityriasis lichenoides (PL) is an uncommon
immunity and endothelial cells bearing HLA class II
self-limited dermatosis which occurs at any age,
antigens have been implicated in the pathogenesis of
particularly in children and young adults(1,2,3). Two
the disease(4/8). Immunogenetic studies on the
variants of the disease are described: a mild chronic
susceptibility to this dermatosis have never been
form referred to as pityriasis lichenoides chronica
accomplished. In this study, besides clinical and
(PLC), and an acute form also known as pityriasis
laboratory evaluation of, we typed HLA class I and II
lichenoides et varioliformis acuta (PLEVA)(2). Despite
antigens in a series of patients presenting with pityriasis
the treatment with antimicrobials are somewhat
lichenoides.
32
HLA and pityriasis lichenoides
2. MATERIAL AND METHODS
2.4. Statistical analysis
2.1. Patients
Comparisons of HLA frequency between pa-
tients and controls was performed using the bicaudal
A total of 21 patients seen at the University
Fisher exact test, correcting the P value according to
Hospital of the Faculty of Medicine of Ribeirão Preto,
the number of HLA specificities. Differences were con-
São Paulo, Brazil, from 1978 to 1993, were retrospec-
sidered significant at P < 0.05. The relative risk (RR)
tively studied. The men to women ratio was 1.6, with
which indicates how many times more often the
ages varying from 10 to 60 years (median 20). Diag-
disease occurs in individuals with the HLA antigen
nosis of pityriasis lichenoides was performed on the
compared to those without it, and the etiologic fraction
basis of clinical and histopathological features.
(EF) which defines the attributable risk at the popula-
2.2. Controls
tion level were also calculated (10).
A total of 100 blood donors from same geo-
3. RESULTS
graphical area and presumably of similar ethnic back-
ground were also typed for HLA antigens.
Most of the cases was observed among chil-
dren and young adults (Figure 1). More than 79% of
2.3. HLA antigens
the cases occurred in Brazilian fall and winter sea-
Mononuclear peripheral cells were isolated us-
sons (April to June and July to September, respec-
ing Ficoll-Hypaque gradient at a density of 1.077 g/l.
tively). With regard to distribution of cutaneous lesions,
B lymphocytes were obtained by adherence to nylon
71% of patients presented typical lesions disseminated
wool. HLA typing was performed by a microlympho-
along the whole body, whereas 19% presented with
cytotoxicity assay(9), using commercially available
lesions restricted to the trunk, neck, and proximal as-
antisera (Pel Freez, Gen Track-USA; Biotest-Ger-
pects of extremities. Only 10% of patients presented
many). A total of 72 HLA class I (A, B) and class II
peripheral lesions confined to upper and lower limbs.
(DR.DQ) specificities were used. Complement was
Fever preceded cutaneous lesions in 14% of patients,
obtained from a pool of normal rabbit sera.
and pruritus was seen along with lesions in 76% of
Sex
6
Total
Female
5
Male
4
s
e
of Cas
3
Number
2
1
0
0 - 5
5 - 10
10 - 15
15 - 20
20 - 50
51 - 90
Age (years)
Figure 1
Figure 1: Bimodal distribution of pityriasis lichenoides cases according to age (years) from 1978 to 1993. Sex distribution is also
shown.
33
NT Foss; LS D Rocha; AMF Roselino & EA Donadi
patients. Hypopigmented macules were
observed in 48% even on the first cuta-
neous examination. Both erythematous
papules with central scales (affecting
HLA-B17 P
also the scalp) and mucous membranes
involvement were seen in 14% of cases,
respectively. Adenomegaly was observed
HLA-B17 C
in 38% of patients. Nineteen percent of
patients had both lesions of PLEVA and
Other HLA
PLC, however, histological features of
typical PLEVA or PLC were observed in
33% and 44% of the cases, respectively.
HLA typing was performed in only
Figure 2: Relative frequency of HLA-B17 in patients and controls in comparison
14 patients. The frequency of HLA-B17
with other HLA-B antigens.
antigen in patients was 36% whereas in
control individuals this antigen was ob-
served only in 1% (Figure 2).
The comparison of the frequency of HLA-B17
4. DISCUSSION
antigen in patients was significantly increased when
compared to controls (P = 0,005). The HLA-B17 anti-
The clinical and laboratory features presented
gen conferred an RR of 55 and an EF of 35. The fre-
by the patients of this series were similar to those re-
quency of HLA class I and II antigens is shown in
ported by other authors(1,2,3), emphasizing the predomi-
(Table I), where the comparisons of HLA class I or II
nance of the disease in children and young adults, and
antigens between patients and controls disclosed no
the occurrence of the disease predominantly in fall and
significant differences.
winter time.
Table I - Frequency (%) of HLA class I (A and B) and class II (DR and DQ) antigens in patients presenting
with pityriasis lichenoides (n = 14) and controls (n = 100). Frequencies observed in controls are shown in
parenthesis. Although 72 specificities were tested, only those seen in patients are shown
HLA-A %
HLA-B %
HLA-DR %
HLA-DQ %
P
C
P
C
P
C
P
C
A1
7
(21)
B7
21
(14)
DR1
36
(26)
DQ1
78
(64)
A2
7
(46)
B15
7
(2)
DR2
28
(31)
DQ2
21
(40)
A3
7
(12)
B17
36
(1)*
DR3
50
(28)
DQ3
57
(44)
A9
7
(27)
B44
36
(16)
DR4
21
(23)
DQ7
36
(37)
A10
14
(27)
B49
7
(6)
DR6
7
(6)
A11
21
(16)
B51
21
(14)
DR7
28
(21)
A28
21
(10)
B60
7
(6)
DR9
14
(2)
A30
40
(4)
DR11
14
(12)
A33
42
(2)
* HLA-B17 corrected P value < 0.005, relative risk = 55, etiologic fraction = 35.
P = patients C= controls
34
HLA and pityriasis lichenoides
Compared to controls, the class I HLA-B17 an-
HLA-B17 antigen upon contact with an yet undeter-
tigen was overrepresented in patients presenting with
mined environmental agent may trigger the develop-
pityriasis lichenoides, conferring high RR and E.F. The
ment of pityriasis lichenoides.
most striking association of a HLA class I antigen with
Increased diffuse expression of HLA-DR
a disease is the observation that HLA-B27+ Caucasian
molecules have been reported on the cell surface of
individuals have 91 times the risk of developing
epidermal keratinocytes of patients presenting with
ankylosing spondylitis than HLA-B27— individuals(11).
pityriasis lichenoides(4/8), suggesting the participation
Besides ankylosing spondylitis, HLA-B27 antigen has
of cells bearing HLA class II molecules in the patho-
also been associated with Reiter’s syndrome and acute
genesis of the disease. However, the comparisons of
anterior uveitis. Particularly, Reiter’s syndrome encom-
the frequency of HLA-DR and HLA-DQ antigens
passes a reactive arthritis seen after episodes of infec-
between patients and controls revealed no significant
tion caused by several enteric and/or urogenital patho-
differences. Although we were not able to define a
gens such as Shigella, Salmonella, Yersinia,
specific association between HLA class II antigen
Campylobacter, Chlamydia and Ureaplasma(12). One
with pityriasis lichenoides, an association with HLA
of the mechanisms of HLA class I molecule associa-
class II specificities cannot be ruled out. In this study,
tion with disease is the mimicry between certain
only serologically defined specificities were tested, per-
epitopes of the causative agents with those of HLA
haps the utilization of more discriminative methods such
molecules(13). Corroborating this hypothesis is the ob-
as the molecular ones may disclose such an
servation of a stretch of 5 amminoacid residues shared
association.
by Shigella strain plasmids and the HLA-B27 mol-
In conclusion, few reports have focused on the
ecule(12,13). Although an infectious agent has not been
study of the immunopathogenic events which are go-
implicated in the pathogenesis of pityriasis lichenoides,
ing on pityriasis lichenoides, and much has to be learned
the involution of cutaneous lesions following an anti-
about them. Notwithstanding, the findings reported here
biotic treatment suggest the participation of an infec-
showed that an HLA class I antigen is overrepresented
tious pathogen. Paralelling the hypotheses which have
in patients. presenting with pityriasis lichenoides, and
been proposed to explain the pathogenesis of Reiter’s
indicate that the HLA-B17 antigen as a susceptible
syndrome, when susceptible individuals carrying the
marker for the development of the disease.
FOSS NT; ROCHA LSD; ROSELINO AMF & DONADI EA.
Pitiríase liquenóide - estudos clínicos e imunogenéti-
cos. Medicina, Ribeirão Preto, 33: 32-36, jan./mar. 2000.
RESUMO:
Modelo de estudo: Estudo de prevalência.
Objetivos: Embora a pitiríase liquenóide seja uma dermatose incomum, 12 casos foram por
nós observados nos últimos três anos. Assim, neste estudo, avaliamos os perfis clínicos e histo-
patológicos dos pacientes com pitiríase liquenóide, atendidos na Divisão de Dermatologia. Além
disso, tipificamos os antígenos HLA de classes I e II nesses pacientes.
Metodologia: Foram estudados 21 pacientes com diagnóstico clínico e histopatológico de
pitiríase liquenóide. As tipificações dos antígenos de histocompatibilidade de classes I e II foram
realizadas, utilizando-se métodos sorológicos.
Resultados: A maioria dos casos ocorreu entre crianças e ou adultos jovens, no outono e
inverno. As lesões típicas de forma disseminada foram as mais freqüentes. Os achados histo-
patológicos mostraram lesões dos tipos agudo e crônico. O antígeno HLA-B17 estava
significantemente aumentado nos pacientes em relação aos controles (P < 0,005).
Conclusões: Embora a etiologia da pitiríase liquenóide não seja conhecida, os achados aqui
relatados mostram que o marcador HLA-B17 é prevalente entre os doentes.
UNITERMOS: Pitiríase Liquenóide . Antígenos HLA. Histologia. Imunogenética.
35
NT Foss; LS D Rocha; AMF Roselino & EA Donadi
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