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 Table of Contents  
Year : 2017  |  Volume : 18  |  Issue : 1  |  Page : 39-42

Multifocal multisystem Langerhans cell histiocytosis

1 Department of Dermatology, Medical College and Hospital, Kolkata, West Bengal, India
2 Department of Dermatology, Mahatma Gandhi Mission Medical College and Hospital, Navi Mumbai, Maharashtra, India
3 Department of Dermatology, K J Somaiya Medical College and Research Centre, Mumbai, Maharashtra, India

Date of Web Publication12-Dec-2016

Correspondence Address:
Anupam Das
“Prerana” 19, Phoolbagan, Kolkata - 700 086, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2319-7250.188442

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We hereby report a case of a male child who presented with multiple brown to red papules and plaques in a seborrheic distribution. Histology and immunohistochemistry findings were consistent with a diagnosis of Langerhans cell histiocytosis with multifocal and multisystem involvement (Letterer–Siwe type). The case is being reported for its rarity.

Keywords: Langerhans cell histiocytosis, multifocal, multisystem

How to cite this article:
Das A, Ardeshna K, Bagadia J. Multifocal multisystem Langerhans cell histiocytosis. Indian J Paediatr Dermatol 2017;18:39-42

How to cite this URL:
Das A, Ardeshna K, Bagadia J. Multifocal multisystem Langerhans cell histiocytosis. Indian J Paediatr Dermatol [serial online] 2017 [cited 2021 May 6];18:39-42. Available from: https://www.ijpd.in/text.asp?2017/18/1/39/188442

  Introduction Top

Langerhans cell histiocytosis (LCH) is a group of disorders caused by the reactive proliferation of bone marrow-derived immature myeloid dendritic cells in the skin and visceral organs.[1] The variant with multifocal and multisystem involvement (Letterer–Siwe type) carries the worst prognosis. In 1868, Paul Langerhans discovered the epidermal dendritic cells which are now referred to as “Langerhans cells.”

  Case Report Top

An 11-month-old irritable male child (weight 4 kg) born of nonconsanguineous parentage presented with itchy scaly lesions over the head, neck, trunk, abdomen, and limbs, present over the preceding 4 months. He had received multiple topical and oral medicines from various physicians, but the resolution was partial. Now, there was a sudden exacerbation of lesions. There was a history of occasional fever, poor feeding, and failure to thrive. There was no history of aural discharge, bleeding from the nose, hematemesis, hematuria, bleeding per rectum, and neurological changes. Family history was noncontributory. General examination showed pallor, pedal edema and generalized nontender lymphadenopathy. Cutaneous examination revealed numerous discrete brownish to red scaly papules and plaques distributed over the scalp, face, chest, abdomen, trunk, and groin (seborrheic distribution). Most of the lesions on the chest and abdomen looked psoriasiform [Figure 1] and [Figure 2]. Palms, soles, nails, and mucosae did not show any abnormality. The systemic survey was significant for the presence of tachypnea, tachycardia, hepatomegaly (4 cm below costal margin), and splenomegaly (2.5 cm below costal margin). Routine laboratory investigations were performed. Important findings were hemoglobin 3.8 g%, total leukocyte count 30,300/mm 3, platelet count 54,000/mm 3, bilirubin 4.2 mg%, and serum glutamic oxaloacetic transaminase: 146 U/L. Ultrasonography of the abdomen showed a diffuse increase in echogenicity suggestive of chronic hepatitis. Bone marrow aspiration findings were within normal limits. X-ray skull did not show any abnormality. Histological examination showed marked epidermotropism of large cells (histiocytes). The cells were large, having abundant pink cytoplasm and reniform nuclei. Besides, there was a mixed infiltrate of lymphocytes, neutrophils, and eosinophils [Figure 3]. On immunohistochemistry, the cells were found to be CD1a and S-100 positive [Figure 4]. Based on clinicopathological correlation and immunohistochemistry findings, a final diagnosis of multifocal multisystem LCH (Letterer–Siwe disease) was done for our patient. The child was admitted to the Department of Pediatrics and therapy with vinblastine and prednisolone was given as per the Histiocyte Society guidelines for LCH with multisystem involvement. In addition, antipyretics, antibiotics, hematinics, etc., were prescribed. Unfortunately, the patient succumbed to acute respiratory distress syndrome within 4 days of admission.
Figure 1: Multiple scaly brown to red papules and plaques over the head, neck, chest, and abdomen

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Figure 2: Close-up view (posterior trunk)

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Figure 3: Photomicrograph showing marked epidermotropism of histiocytes. In addition, infiltrate of lymphocytes, neutrophils, and eosinophils seen. Note the abundant pink cytoplasm and reniform nuclei of the histiocytes (H and E, ×400)

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Figure 4: Immunohistochemistry showing CD1a (a) and S-100 (b) positivity

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  Discussion Top

LCH is a rare heterogeneous group of disorder characterized by an accumulation or clonal proliferation of Langerhans-type cells that share immunophenotypic and ultrastructural similarities with antigen-presenting LCs.[2] For this reason, it was hypothesized that the disease originated from epidermal LCs. However, more recent studies using cell-specific gene expression profiling suggest that LCH arises from bone marrow-derived immature myeloid dendritic cells rather than from epidermal LCs.

The current nomenclature by the Histiocyte Society and the World Health Organization separates LCH disorders from non-LCH histiocytic syndromes and malignancies. LCH is divided into three groups: “unifocal (eosinophilic granuloma), multifocal unisystem (Hand–Schüller–Christian disease), and multifocal multisystem (Letterer–Siwe disease).”[3]

LCH has varied clinical manifestations and an unpredictable course. Multifocal multisystem LCH, earlier called Letterer–Siwe disease (derived from the names of Erich Letterer and Sture Siwe), is a rapidly-progressing disseminated disease involving LCs proliferation in many tissues. It generally affects children under 2 years of age and has the poorest prognosis, consistent with our case. Skin involvement is in the form of recurrent pyoderma such as lesions with crusting and scaling, vesiculopustular and purpuric eruption occurring in crops over the face, scalp, trunk, and intertriginous area, resembling seborrheic dermatitis. Intraoral hemorrhage, gingivitis, loose teeth, floating teeth, precocious eruption of teeth and ectopic teeth also may be seen. Lesions may affect a variety of other systems, including bones (skull, ribs, humerus, and vertebra), gastrointestinal tract (GIT) involvement (liver, spleen), lymph nodes, bone marrow, central nervous system, and less frequently lungs.[4] The differential diagnosis for LCH may include other histiocytic lesions (Rosai–Dorfman disease, Erdheim–Chester disease, juvenile xanthogranuloma), dendritic neoplasm (follicular dendritic cell sarcoma and interdigitating dendritic cell sarcoma), lymphoma, and LC sarcoma.[5]

The classical histopathologic feature of LCH is the presence of lesional histiocytes of LC phenotype, with varying proportions of T-lymphocytes, eosinophils, macrophages, and multinucleated giant cells. The presence of Birbeck granules on electron microscopy or demonstration of CD1a and/or Langerin (CD207) in the lesion is the current gold standard for the diagnosis of LCH.[6] Often, cutaneous lesions may be the only clinical finding, and in such cases, diagnosis is performed on the basis of the presence of characteristic S-100 positive LCs.[7]

Therapy decision is based on whether the high- or low-risk organs are involved and whether the disease is single system or multisystem. Risk organs and their involvement were defined according to modified Lahey criteria as follows:[4]

  • Hematopoietic: Anemia and/or leukopenia and/or thrombocytopenia
  • Liver: Enlargement >3 cm below the costal margin, dysfunction, or both
  • Spleen: Enlargement >2 cm below the costal margin
  • Lung: Typical changes via high-resolution computed tomography, histopathological diagnosis, or both.

As per these criteria, our patient had anemia, thrombocytopenia, hepatomegaly (4 cm below costal margin), and splenomegaly (2.5 cm below costal margin).

Localized skin disease are not required to treat always because, in many cases (typically in infants), the lesions will regress spontaneously. For multisystem LCH, the Histiocyte Society suggests that the treatment duration of 12 months reduces the risk of reactivation compared with 6 months of treatment.[8] Patients with multisystem LCH without any risk organ involvement, and those with risk organ involvement but who respond to standard initial therapy, have an excellent chance of long-term survival. Prednisone and vinblastine combination has been proven to be an effective treatment with minimal toxicity, and hence, it is the standard initial therapy for all patients in whom systemic therapy is indicated.[9],[10] Patients with risk organ involvement who do not respond within the first 6 weeks of therapy, especially those with evident clinical progression, have an unfavorable prognosis.[9],[11],[12] For those, an early intensification of therapy is required. Few treatment options exist for patients with recurrent or refractory multisystem or multiorgan involvement; however, promising results are reported with the combination of cladribine and cytarabine [13] and stem cell transplantation. Successful treatment with thalidomide has also been reported.[14]

Causes of mortality include disease progression, infectious complications, organ failure, and acute nonlymphoblastic leukemia. The death in our patient was attributed to respiratory failure. The most commonly reported permanent consequences are endocrine (diabetes insipidus, growth hormone deficiency), orthopedic (scoliosis, facial asymmetry), and auditory (hearing loss). Neurocognitive (cerebellar ataxia, learning difficulties), pulmonary (fibrosis, emphysema), and hepatic sequelae (sclerosing cholangitis, cirrhosis) are rare but may cause reduction in quality of life and significant morbidity. Recent discoveries of mutations in BRAF and MAP2K1 genes could change the therapeutic approach in LCH from chemotherapy to targeted therapy, giving better prognosis and a lower rate of long-term therapy-related adverse events.[4]

Declaration of Patient Consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of Interest

There are no conflicts of interest.

  References Top

Singh T, Satheesh CT, Appaji L, Aruna Kumari BS, Mamatha HS, Giri GV, et al. Langerhan's cell histiocytosis: A single institutional experience. Indian J Med Paediatr Oncol 2010;31:51-3.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
Kusuma Kumary P, Priyakumari T, Chellam VG, James FV, Nair MK. Langerhans cell histiocytosis in children less than 2 years of age. Indian Pediatr 1999;36:29-36.  Back to cited text no. 2
Suresh T, Ankur T, Kshama T, Rachita N. Histiocytosis. In: Sacchidanand S, Oberai C, Inamadar A, Editors. IADVL Textbook of Dermatology. 4th ed. Mumbai: Bhalani Publishing House; 2015. pp. 2256.  Back to cited text no. 3
Grana N. Langerhans cell histiocytosis. Cancer Control 2014;21:328-34.  Back to cited text no. 4
Harmon CM, Brown N. Langerhans cell histiocytosis: A clinicopathologic review and molecular pathogenetic update. Arch Pathol Lab Med 2015;139:1211-4.  Back to cited text no. 5
Aruna DR, Pushpalatha G, Galgali S, Prashanthy. Langerhans cell histiocytosis. J Indian Soc Periodontol 2011;15:276-9.  Back to cited text no. 6
[PUBMED]  Medknow Journal  
Punia RS, Bagai M, Mohan H, Thami GP. Langerhans cell histiocytosis of skin: A clinicopathologic analysis of five cases. Indian J Dermatol Venereol Leprol 2006;72:211-4.  Back to cited text no. 7
Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, et al. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood 2013;121:5006-14.  Back to cited text no. 8
Narula G, Bhagwat R, Arora B, Banavali S, Pai S, Nair C, et al. Clinico-biologic profile of Langerhans cell histiocytosis: A single institutional study. Indian J Cancer 2007;44:93-8.  Back to cited text no. 9
[PUBMED]  Medknow Journal  
Minkov M, Steiner M, Pötschger U, Aricò M, Braier J, Donadieu J, et al. Reactivations in multisystem Langerhans cell histiocytosis: Data of the International LCH Registry. J Pediatr 2008;153:700-5, 705.e1-2.  Back to cited text no. 10
Minkov M, Grois N, Heitger A, Pötschger U, Westermeier T, Gadner H; DAL-HX Study Group. Response to initial treatment of multisystem Langerhans cell histiocytosis: An important prognostic indicator. Med Pediatr Oncol 2002;39:581-5.  Back to cited text no. 11
Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, et al. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr 2001;138:728-34.  Back to cited text no. 12
Bernard F, Thomas C, Bertrand Y, Munzer M, Landman Parker J, Ouache M, et al. Multi-centre pilot study of 2-chlorodeoxyadenosine and cytosine arabinoside combined chemotherapy in refractory Langerhans cell histiocytosis with haematological dysfunction. Eur J Cancer 2005;41:2682-9.  Back to cited text no. 13
Shahidi-Dadras M, Saeedi M, Shakoei S, Ayatollahi A. Langerhans cell histiocytosis: An uncommon presentation, successfully treated by thalidomide. Indian J Dermatol Venereol Leprol 2011;77:587-90.  Back to cited text no. 14
[PUBMED]  Medknow Journal  


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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