ARTICLE
Auteur(s) : Achiléa L
Bittencourt1, Maria de Fátima Oliveira2,
Neide Ferraz2, Maria das Graças Vieira1,
André Muniz2, Carlos Brites3
1Department of Pathology, Hospital Universitário
Prof. Edgard Santos, Federal University of Bahia , Salvador, Bahia,
Brazil
2Internal Medicine, Hospital, Universitário Prof. Edgard
Santos, Federal University of Bahia , Salvador, Bahia, Brazil
3Laboratory of Retrovirology, Hospital Universitário
Prof. Edgard Santos, Federal University of Bahia , Salvador, Bahia,
Brazil
accepté le 13 Septembre 2005
Salvador (Bahia, Brazil) is an endemic area for HTLV-I. The overall
prevalence of HTLV-I infection in the general population has been
estimated at 1.76% [1]. Carriers of HTLV-I may develop many
diseases, such as adult T-cell leukemia/lymphoma (ATL),
HTLV-I-associated myelopathy/tropical spastic paraparesis
(HAM/TSP), a chronic neurological disease, and infective dermatitis
associated with HTLV-I (IDH).Twenty-three cases of IDH have been
reported in this state, some of them associated with the juvenile
form of HAM/TSP [2, 3].IDH is a form of infected and recurrent
dermatitis that affects children infected with HTLV-I. The lesions
are erythematous, scaly and crusted, and are more frequently
located on the scalp and on the retroauricular, cervical, perioral,
inguinocrural and peri-nasal regions. The patients present mild to
moderate pruritus, and chronic nasal secretion/crusts on the
nostrils. IDH is generally associated with Staphylococcus aureus
and/or Streptococcus beta haemolyticus infection and may progress
to ATL and to HAM/TSP [2-4]. In 1998, La Grenade et al. [4]
proposed the major and minor criteria for diagnosis of this
disease.No cases of late-onset IDH have yet been described. This
report presents the first adult-onset cases.
Patients and methods
Demographical and clinical data were collected from patients and
are shown in table 1( Table 1 ).
Clinical, dermatological and neurological examinations were carried
out. The diagnosis of IDH was made according to previously
established criteria [2, 4]. A differential diagnosis between IDH
and atopic dermatitis (AD) was made based on pre-existing criteria
[5, 6] and between IDH and seborrheic dermatitis (SD) based on
clinical aspects [7]. Both patients were submitted to routine
laboratory studies, to skin culture for bacterial pathogens and to
direct mycological examination. In the patient with neurological
manifestations, cerebrospinal fluid (CSF) examination was performed
and evaluation of motor dysfunction was carried out using Osame’s
motor disability score (OMDS) [8] and expanded disability status
score (EDSS) [9]. Antibodies to HTLV-I/II were detected by
diagnostic enzyme-linked immunosorbent assay (ELISA) and confirmed
by Western Blot, which is capable of discriminating between HTLV-I
and HTLV-II (HTLV Blot 2.4, Genelab Singapore). Serology for HIV
was also performed. Punch skin biopsies were performed on the scalp
lesions and in Case 2 another biopsy was also obtained from the
abdominal lesion. The biopsies were fixed in 10% buffered formalin,
the blocks were embedded in paraffin, and histological sections
were stained with hematoxylin and eosin. The immunohistochemical
study of the inflammatory cells was performed in paraffin-embedded
sections using a standard streptavidin-biotin-peroxidase technique
and the following antibodies: CD45RO, CD3, CD8, CD20 and CD79a
(Dako, Glostrut, Denmark), and CD4 (Novocastra, Newcastle, UK). The
immuno-phosphatase technique (Streptavidin Biotin System) for
identification of cytotoxic granules was performed using the
anti-granzyme B, anti-perforin (Novocastra) and anti-TIA-1
(Immunotech, Marseille, France) antibodies. The natural killer
phenotype was identified using the same technique and the CD57
(Novocastra) antibody. The cell counts were made using a
semi-quantitative assessment. The percentage of the CD4+, CD8+ and
CD57+ cells in the inflammatory infiltrate was calculated using
counts carried out in five high magnification fields (640X). Both
patients gave their signed informed consent.
Table 1 Data of the patients
|
Cases
|
Sex/Color
|
Age (y)
|
Duration of IDH
|
HAM/TSP
|
Distribution of lesions
|
|
1
|
F/W
|
49
|
0.6 y
|
+
|
Scalp, forehead, eyebrows, nostrils, peri-oral, eyelids, neck,
abdomen, back and infra-mammary and anticubital flexures.
|
|
2
|
F/W
|
45
|
11 y
|
–
|
Scalp, forehead, ears, posterior aspect of neck, abdomen, back,
axilla, groin and infra-mammary and popliteal flexures. Presence of
retroauricular fissures.
|
Results
Both patients had been breast-fed, but the mother of Case 2 was
HTLV-I negative. Neither had received blood transfusions and they
had no history of promiscuity (less than 5 partners). Neither
patient had a history of childhood eczema. They were HTLV-I
positive and HIV negative and presented positive culture for
Staphylococcus aureus and negative mycological direct examination.
The patients complained of mild pruritus. The skin lesions in both
patients were erythematous, scaly, and exudative with adherent
yellowish crusts (figures 1 and 2). The distribution of the lesions
is shown in table 1. Case 1 also presented lesions in the nostrils
(( figure 2 ))
and blepharoconjunctivitis. The skin disease was more severe in
Case 2 with an extensive lesion resembling a bandage on the lower
trunk (( figure
3 )). Good response of the skin lesions to
sulfamethoxazole/trimethoprim was obtained in both patients,
although there was a relapse following withdrawal of the drugs.
Association with HAM/TSP was observed in Case 1. This patient
reported that her difficulty in walking occurred simultaneously
with the dermatitis. The cerebrospinal fluid of this patient tested
positive for HTLV-I and negative for syphilis, toxoplasmosis,
cysticercosis, and schistosomiasis. The patient presented
paraplegia, marked hyperreflexia and spasticity, urinary urgency
and constipation. She presented OMDS: 10 and EDSS: 8.
Histopathology
Psoriasiform acanthosis, parakeratosis, focal spongiosis, basal
vacuolar degeneration and superficial perivascular infiltration of
lymphocytes were observed in both cases (( figure 4 )). Some plasma
cells and a few neutrophils were also seen. In addition, single
lymphocytes lining the basal layer were seen in some areas (( figure 5 )). One focus
of epidermotropism associated with moderate degree spongiosis was
seen in Case 1. In this case, an area of Kogoj’s spongiform pustule
was also observed. The majority of the inflammatory cells were CD3+
CD8+, some of them present along the basal layer (( figure 6 )), but they were
TIA-1, granzyme B and perforin negative. The percentage of CD4+ and
CD8+ cells was 35% and 47% in Case 1, and 60% and 30% in Case 2,
respectively. The frequency of CD57+ cells varied from 12% to 19%.
Some T cells in both cases were CD8+ CD57+, often present along the
basal layer.
Discussion
The cases here reported fulfilled the major criteria of La Grenade
et al. [4] for diagnosis of IDH, except for the absence of crusting
of the nostrils in one case. The absence of this criterion does not
invalidate the diagnosis of IDH because it may be present
intermittently [2]. Moreover, some unequivocal cases of IDH fail to
present this feature [2, 10].
The diagnosis of IDH is mainly clinical and it is necessary to
differentiate it from atopic dermatitis (AD) and seborrheic
dermatitis (SD). In IDH, the morphology and distribution of the
lesions are similar in part to those of AD, although in IDH the
lesions are more marked, are exudative and are more exuberantly
infected. Moreover, the pruritus observed in AD is more marked than
that found in IDH [6].
Although sometimes occurring in the same regions, the lesions in
IDH, in contrast to the lesions found in cases of SD, are more
exudative and present yellowish crusts. In SD, the lesions are
covered by greasy scales [7]. Pityrosporum yeasts, known to occur
frequently in SD [7], were not observed during direct examination
of the lesions in either of the two cases reported here. In
addition the good response to sulfamethoxazole/trimethoprim in IDH
is not characteristic of SD.
Although the Kogoj spongiform pustule seen in Case 1 is highly
suggestive of psoriasis, it may occur in some superficial forms of
mycosis and in infected dermatoses [11]. In addition, the clinical
aspects of the cases presented are different from those of
psoriasis.
Considering that IDH may evolve to lymphoma [4], a differential
diagnosis must be made with mycosis fungoides. Microscopically,
linearly arranged, single lymphocytes were seen focally along the
basal layer in both cases. It is known that this architectural
pattern may be observed in mycosis fungoides but it is also seen,
although less frequently, in inflammatory dermatosis [12] including
IDH [13]. However, in all the biopsies carried out in these two
cases, atypical lymphocytes or mitoses were not observed. According
to many authors [12, 14, 15], to reach a diagnosis of mycosis
fungoides, even in the early phase, it is necessary to identify
atypical cells rather than emphasize architectural aspects.
However, these patients have to be followed-up carefully.
As in cases of pediatric IDH, the cases reported here do not
present cytotoxic granules in the CD8+ cells [16], indicating that
these lymphocytes are non-activated cytotoxic cells. In contrast,
in AD and SD the T lymphocytes are predominantly of the CD4+ helper
cell phenotype [17, 18]. Moreover, in AD granzyme B+ and perforin+
granules are present in the epidermis and dermis and may contribute
to skin inflammation [19].
CD57+ cells represent a subset of T cell that increases in
number in some conditions such as acquired immune deficiency
syndrome, rheumatoid arthritis and after organ transplantation
[20]. These cells have also been observed in most cases of
childhood IDH (13). The distribution of the CD57+ T cells in the
present cases suggests that they play a role in the inflammatory
process. It has been reported that CD57+ T cells produce larger
amounts of interferon-gamma [21].
These cases were considered adult-onset IDH because: 1) the
morphology and distribution of lesions were similar to those found
in childhood infective dermatitis; 2) in neither case was there a
history of childhood eczema; and 3) the immunohistochemical
findings were identical to those observed in childhood IDH and
quite different from those seen in AD and SD.
The association of IDH with HAM/TSP has been rarely reported and
only in the juvenile form of this myelopathy [3]. In both diseases,
the inflammatory infiltrate is composed predominantly of T
lymphocytes. In HAM/TSP, CD4+ and CD8+ cells are found in the early
stages of disease, however, CD8+ cells predominate over CD4+ cells
in the other stages of disease [22]. According to the
cytolytic-pathogenetic hypothesis for this disease, the CD8+ cells
play an important role in tissue lesions that result in destruction
and atrophy [23]. With respect to IDH, there is no destruction of
the skin tissues and a predominance of CD8+ cells is observed in
the inflammatory infiltrate. However perforin+ and granzyme B+
granules are not present in these cells, therefore they are not
activated T cells [13]; hence IDH lesions cannot therefore be
explained by a cytotoxic mechanism.
We conclude that IDH may appear in adulthood and can be
associated with HAM/TSP. The differential diagnosis between IDH and
AD and SD is clinical and in accordance with the literature and our
previous findings, also immunohistochemical.
Acknowledgments
The research was supported by a grant from Conselho Nacional de
Pesquisas (CNPq) and Fundação de Apoio a Pesquisa na Bahia
(FAPESB).
References
1 Dourado I, Alcantara LC, Barreto ML, da Gloria
Teixeira M, Galvão-Castro B. HTLV-I in the general
population of Salvador, Brazil: a city with African ethnic and
sociodemographic characteristics. J Acquir Immune Defic Syndr 2003;
34: 527-31.
2 De Oliveira MF, Brites C, Ferraz N,
Magalhães P, Almeida F, Bittencourt AL. Infective
dermatitis associated with the human t-cell lymphotropic virus type
I HTLV-I in Salvador, Bahia, Brazil. Clin Infect Dis 2005; 40:
e90-e96.
3 Primo JRL, Bittencourt AL, Oliveira MFS,
Moreno O, Machado M, Brites C. Infective dermatitis
and juvenile HTLV-I-associated myelopathy/tropical spastic
paraparesis (HAM/TSP). Clin Infect Dis 2005; 41: 535-41.
4 La Grenade L, Manns A, Fletcher V,
Carberry C, Hanchard B, Maloney EM, Cranston B,
Williams NP, Wilks R, Kang EC, Blattner WA.
Clinical, pathologic, and immunologic features of human
T-lymphotrophic virus type I-associated infective dermatitis in
children. Arch Dermatol 1998; 134: 439-44.
5 Hanifin JM, Rajka G. Diagnostic features of atopic
dermatitis. Acta Derm Venereol 1980; 92: 44-7.
6 Holden CA, Parish WE. Atopic dermatitis. In:
Champion RH, Bourton JL, Burns DA,
Breathnach SM, eds. Rook/Wilkinson/Ebling, Textbook of
Dermatology. London: Blackwell Scientific Publications, 1998:
681-708.
7 Burton JL, Holden CA. Eczema, Lichenification and
Prurigo. In: Champion RH, Bourton JL, Burns DA,
Breathnach SM, eds. Rook/Wilkinson/Ebling, Textbook of
Dermatology. London: Blackwell Scientific Publications, 1998:
629-80.
8 Izumo S, Goto I, Itoyama Y, Okajima T,
Watanabe S, Kuroda Y, Araki S, Mori M,
Nagataki S, Matsukura S, Akamine T, Nakagawa M,
Yamamoto I, Osame M. Interferon-alpha is effective in
HTLV-I-associated myelopathy: a multicenter, randomized,
double-blind, controlled trial. Neurology 1996; 46: 1016-21.
9 Kurtzke JF. Rating neurologic impairment in multiple
sclerosis: an expanded disability status scale (EDSS). Neurology
1983; 33: 1444-52.
10 Suite M, Jack N, Basdeo-Maharaj K,
Edwards J, White F, Blattner W, Bartholomew C.
Infective Dermatitis In Trinidad And Tobago. AIDS Res Hum
Retroviruses 1994; 10: 447.
11 Mobini N, Toussaint S, Kamino H. Non
infectious erithematous, papular, and squamous diseases. In:
Elder DE, Elenitsas R, Johnson BL, Murphy GF,
eds. Lever’s histopathology of the skin. Phyladelphia: Lippincott
Williams & Williams, 2004: 179-214.
12 Santucci M, Biggeri A, Feller AC,
Massi D, Burg G. Histologic Criteria for Diagnosing Early
Mycosis Fungoides. Am J Surg Path 2000; 24: 40-50.
13 Bittencourt AL, Oliveira MF, Brites C,
Weyenbergh JV, Vieira MGS, Iguaracyra Araújo I.
Histopathological and immunohistochemical studies of infective
dermatitis associated with HTLV-I. Eur J Dermatol 2005; 15:
26-30.
14 Tok J, Szabolcs MJ, Silvers DN, Zhong J,
Matsushima AY. Detection of clonal T-cell receptor gama chain
gene rearrangements by polymerase chain reaction and denaturing
gradient gel electrophoresis (PCR/DGGE) in archival specimens from
patients with early cutaneous T-cell lymphomas: Correlation of
histologic findings with PCR/DGGE. J Am Acad Dermatol 1998; 38:
453-60.
15 Smoller BR, Bishop K, Glusac E, Kim YH,
Hendrickson M. Reassessment of histologic parameters in the
diagnosis of mycosis fungoides. Am J Surg Pathol 1995; 19:
1423-30.
16 Lugovic L, Lipozenocic J, Jakic-Razumovic J.
Atopic dermatitis: immunophenotyping of inflammatory cells in skin
lesions. Int J Dermatol 2001; 40: 489-94.
17 Watanabe K, Kondo N, Futukomi O,
Takami T, Agata H, Orii T. Characterization of
infiltrating CD4+ cells in atopic dermatitis using CD45R and CD29
monoclonal antibodies. Ann Allergy 1994; 72: 39-44.
18 Oranje AP, van Joost T, van Reede EC,
Vuzevski VD, Dzoljic-Danilovic G, Kate FJ,
Stolz E. Infantile seborrhoeic dermatitis. Morphological and
immunopathological study. Dermatologica 1986; 172: 191-5.
19 Yawalkar N, Schmid S, Braathen LR,
Pichler WJ. Perforin and granzyme B may contribute to skin
inflammation in atopic dermatitis and psoriasis. Br J Dermatol
2001; 144: 1133-9.
20 Ohkawa T, Seki S, Dobashi H, Koike Y,
Habu Y, Ami K, Hiraide H, Sekine I. Systematic
characterization of human CD8+ T cells with natural killer cell
markers in comparison with natural killer cells and normal CD8+ T
cells. Immunology 2001; 103: 281-90.
21 Van den Hove LE, Van Gool SW, Vandenberghe P,
Boogaerts MA, Ceuppens JL. CD57+/CD28- T cells in
untreated hemato-oncological patients are expanded and display a
Th-1 type cytokine secretion profile, ex-vivo cytolytic activity
and enhanced tendency to apoptosis. Leukemia 1998; 12: 1573-82.
22 Izumo S, Ijichi T, Higuchi I, Tashiro A,
Takahashi K, Osame M. Neuropathology of HTLV-I Associated
Myelopathy – A Report of Two Autopsy Cases. Acta Paediatr Jpn 1992;
34: 354-8.
23 Manns A, Hisada M, La Grenade L. Human
T-Iymphotropic virus type I infection. Lancet 1999; 353:
1951-8.
|
Version imprimable
Version PDF
