Self-healing langerhans cell histiocytosis (Hashimoto-Pritzker disease): two TUnisian cases
H. Belhadjali, M. Mohamed, H. Mahmoudi, M. Youssef, A. Moussa, S. Achour Chouchane, C. Chouchane, A. Zakhama and J. Zili
A B S T R A C T-
"Self-healing" Langerhans cell histiocytosis (SHLCH) is a rare self-limited variant of Langerhans cell histiocytosis that presents at birth or during the neonatal period. It was first described by Hashimoto and Pritzker in 1973. Subsequently, more than 70 cases have been reported in the literature. Regarding age of onset, SHLCH should be divided into congenital SHLCH and rare late-onset type. We report here two additional cases of SHLCH in Tunisian infants. We emphasize the need for long-term follow-up in such patients.
Introduction
"Self-healing" Langerhans cell histiocytosis (SHLCH) is a rare self-limited variant of Langerhans cell histiocytosis (LCH) that presents at birth or during the neonatal period (1). It was first described by Hashimoto and Pritzker in 1973 (1). Subsequently, more than 70 cases have been reported in the literature (2). We report here two additional cases of SHLCH in Tunisian infants.
Case 1
A male infant, born at term after an uncomplicated pregnancy, presented at the age of 1 month with multiple skin lesions since birth, consisting of yellowish papules ranging in size from 5 to 15 mm in diameter, and sometimes with ulcerations and scabs. The lesions were distributed over the trunk, lower limbs, and soles (Fig. 1 and Fig. 2). The child was otherwise healthy with no involvement of the mucous membranes. A skin
biopsy revealed a massive infiltration of mononuclear cells in the superficial and deep dermis surrounding the sweat glands. The cells had eccentric, pale, reniform nuclei, and abundant eosinophilic cytoplasm. Figure 3. Occasional eosinophils were also present. Infiltrating histiocytic cells made micro-abscess-like clusters within the epidermis, which was ulcerated. Figure 3.. Immu-nohistochemistry demonstrated that most infiltrating cells were positive for S-100 protein and CD 1a antigen. Based on histological and immunohistochemical findings, we concluded that the lesions should be categorized as LCH.
Systemic evaluation of the child, including complete blood counts, serum biochemistry, liver function tests, radiographic skeletal survey, ultrasound of the abdomen, and bone marrow aspiration, produced normal results. Due to the absence of involvement of the internal organs, we decided to observe the course without
K E Y WORDS
histiocytosis, Langerhans cell self-healing, Hashimoto-Pritzker disease, childhood
aggressive treatment. The skin lesions regressed, and after a few weeks they completely disappeared. By 4 years of age the child was symptom-free with no signs of a relapse. Based on the clinical pictures, histopathologic and immunohistochemical features, and a self-healing course, the diagnosis of congenital SHLCH was established.
Case 2
A 4-month-old girl presented at our dermatology department with a history of multiple papulonodules on the face and trunk from 20 days of age. She was born at term after an uncomplicated pregnancy. The physical examination revealed multiple 5 to 20 mm brownish-red papulonodules with a smooth surface distributed over the face and trunk (Fig.4). The mucous membranes, palms, and soles were spared. The child was otherwise healthy and the physical examination was normal. Due to the nodular lesions, a diagnosis of juvenile xanthogranuloma was considered. A skin biopsy showed a dense infiltrate of histiocytic cells in the superficial and deep dermis, which were also invading the subcutaneous fat. The cells had vesicular, sometimes reniform nuclei, and foamy cytoplasm. Sparse eosinophils were also seen and there was no epidermo-tropism. On immunohistochemical analysis, most of the cells were positive for S-100 protein and CD 1a antigen (Fig. 5). Systemic evaluation of the tests (blood counts, serum biochemistry, liver function tests, a radiographic skeletal survey, ultrasound of the abdomen, and bone marrow aspiration) were normal. We decided to simply observe the child. Although the skin lesions completely disappeared by the age of 5 months, at the age of 8 months we observed a recurrence of a small number of them. A new systemic evaluation of the child produced normal results. All the skin lesions disappeared within a few weeks, leaving behind pigmented scars. After an 8-year follow-up, the child was symptom-free with no signs of further relapses. The diagnosis of late-onset SHLCH was confirmed.
Discussion
Langerhans cell histiocytosis (LCH) is a generic term that identifies several clinical diseases characterized by proliferation of distinctive cells that are S-100- and CD la-positive and contain Birbeck granules in their cytoplasm (3-4).
More than 70 cases of SHLCH have been reported in the literature (2). The real incidence of this disorder may be underreported due to its high rate of spontaneous resolution and failure of clinical recognition (5).
Regarding the age of onset, SHLCH should be di-
Table 1. Case reports of late-onset SHLCH in the literature.
Series Number of cases Age at onset	
Jang et al. (6) 3	1, 2, 7 months
Hashimoto et al. (7) 1	17 days
Masouye et al. (8) 1	2 months
Campourcy et al. (9) 1	18 months
Weiss et al. (10) 1	7 months
Nakahighashi et al. (2) 1	8 years
Our report 1	20 days
vided into the common type, namely congenital SHLCH, as observed in our first case, and a rare late-onset type. To the best of our knowledge, only 8 cases of late-onset SHLCH have been reported in the literature (2, 6-10). Late-onset SHLCH cases are summarized in Table 1.
SHLCH is clinically characterized by skin lesions consisting of multiple, disseminated, firm, red-brown, painless papulonodules affecting the entire body, but with a predilection for the cephalic area and the scalp (4, 11). Palms and soles (4, 11), as observed in our first case, were also reported. SHLCH does not involve the internal organs. A few cases of SHLCH also had bone marrow (7), bone (12), lung (13), and eye (14) involvement. Therefore, in all cases of SHLCH, a thorough systemic evaluation is warranted to exclude visceral disease (4). In both our cases, lesions were restricted to the skin.
Histologically, SHLCH demonstrates massive dermal infiltrates of pleomorphic histiocytes with abundant eosinophilic ground-glass cytoplasm (8) and reni-form nuclei with irregular contours (15). As observed in our second case, xanthomatous features, eosinophils, lymphocytes, and neutrophils are also common (16). Multinucleated giant cells may also exist (16, 17). Infiltrating histiocytic cells can extend into the epidermis and consequently cause ulcerations, as observed in our first case (11, 17). Moreover, in our second case, subcutaneous fat showed the same infiltrate type as the dermis (mainly as nodular lesions).
The cells in the infiltrate were S-100- and CD 1a-positive to immunolabelling. They can also be positive for macrophage and/or monocyte lineage (11).
Electron microscopic evaluation was not performed, but it can reveal Birbeck granules or laminated dense bodies inside 10 to 30% of the histiocytes (17).
The most interesting feature of Hashimoto-Pritzker disease is its spontaneous involution, usually within 1 to 3 months (17). Spontaneous regression may end with hypopigmented, pigmented, or atrophic scars (11).
Figure 1. Papules distributed over the trunk and Figure 2. Two papules on the left sole. Case 1. lower limbs. Case 1.
Possible relapses either in the skin (as observed in our second case) or at extracutaneous sites have been reported up to 4 years after the initial disappearance of the congenital lesions (3, 18, 19, 20, 21). A close follow-up is therefore necessary (11).
SHLCH should be differentiated from the malignant
Figure 4. Brownish-red nodule on the face. Case 2.
Figure 3. Skin biopsy specimen showing histiocytic cells admixed with rare eosinophils (magnification x 400)
form of other LCHs, such as Letterer-Siwe disease. However, the healthy general condition, the lack of multiorgan involvement, and the spontaneous regression of the lesions (1, 4) suggest the diagnosis of SHLCH. It should also be differentiated from other histiocytic disorders known to regress spontaneously, namely ju-
Figure 5. The proliferating histiocytic cells were positive for anti-CD 1a. Case 2.
venile xanthogranuloma (4).
The treatment protocol for single-system LCH involvement, as in SHLCH, is "wait and watch" for spon-
relapses, most clinicians follow the wait-and-watch policy with good results (18, 20). SHLCH patients with multisystem involvement may also show spontaneous
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AUTHORS' Hichem Belhadjali, MD, Department of Dermatology, Fattouma ADDRESSES Bourguiba Hospital, Monastir 5000, Tunisia, corresponding author,
E-mail: belhadjalihichem@yahoo.fr Mariem Mohamed, MD, same address Houda Mahmoudi, MD, same address Monia Youssef MD, same address Adnene Moussa, MD, same address Sonia Chouchane, MD, same address Achour Chouchane, MD, same address Abdefatah Zakhama, MD, same address Jammeleddine Zili, MD, same address