Langerhans Cell Histiocytosis
A 17-year-old male presented with anogenital erosions of 2 years’ duration, extending from the perianal region to the scrotum. Based on the appearance of the lesions, the teenager had been treated with valacyclovir for presumed herpes simplex virus (HSV) infection, despite negative HSV test results.
The patient was admitted for pain management and intravenous acyclovir. No vesicles or penile involvement were noted at the time of admission, and he denied sexual activity. The adolescent incidentally reported polyuria and polydipsia beginning 2 weeks previously, with a daily intake of up to 20 liters at admission. His medications included only valacyclovir, and he had no known allergies. Based on inconsistencies in the appearance and history of the lesions, dermatology was consulted, and the lesions were biopsied.
The results of the biopsy revealed significant histiocytic infiltration in the dermis, with pathology test results confirming the presence of Langerhans cells. Results of magnetic resonance imaging were significant for a lack of normal neurohypophyseal T1 brightening and thickening of the pituitary infundibulum. The diagnosis of Langerhans cell histiocytosis (LCH) with associated diabetes insipidus (DI) was confirmed. Results of a skeletal survey, liver function tests, and blood counts were normal, indicating no other areas of involvement.
LCH is a clonal proliferative disease of Langerhans cells, antigen-presenting cells of the epidermis and mucosa. It is a rare disorder that commonly is characterized by osteolytic bone lesions demonstrating infiltration with histiocytes. Extraskeletal infiltrations also can appear in the skin, lymph nodes, lungs, thymus, liver, spleen, bone marrow, or central nervous system. The most common cutaneous presentation in infants is a seborrheic-like eruption of the scalp. Genital ulcerations are rare, with 24 of the 25 reported cases in adult women.1 Approximately 25% of LCH cases have associated DI, which usually is irreversible but controllable with vasopressin.
Differential diagnosis for LCH presenting with cutaneous lesions of the genitals includes HSV, as well as varicella and erythema toxicum neonatorum, since vesicular lesions and ulcerations in LCH are most common during infancy. Cutaneous involvement also can mimic vasculitis, cutaneous lymphoma, and cutaneous involvement with Erdheim-Chester disease. Other diagnoses to consider include dermatillomania, cutaneous Crohn disease, and Behçet syndrome.
The diagnosis ultimately is made based on results of bone or skin lesion biopsy. Pathology confirms the presence of Langerhans cells with positive immunohistochemical staining for CD1a and CD207, or identification of Birbeck granules on electron microscopy. LCH must be distinguished histologically and immunophenotypically from other histiocytic and dendritic cell disorders, metastatic neoplasms, hemophagocytic lymphohistiocytosis, and macrophage activation syndromes.
Treatment depends on the extent of lesions. Single-organ involvement may be self-limiting and require no treatment or may require chemotherapy, systemic corticosteroids, excision of lesion, and therapy directed at the target organ.2 In multisystem LCH, the Histiocyte Society recommends 6 weeks of induction treatment with vinblastine weekly and oral prednisone, repeated for a second induction if the response is incomplete.3 Once no further disease is found, maintenance therapy commences for 12 months, with vinblastine every 3 weeks, and prednisone orally for 5 days every 3 weeks. Follow-up is required for 5 to 10 years, monitoring for hormone deficiency, DI, malignancies, or complications at lesion sites.4
Our patient underwent induction treatment with vinblastine and prednisone and is now in the maintenance phase, receiving prednisone every 3 weeks and vinblastine on day 1 of the 21-day cycles. Because of their depth, his lesions required healing via secondary intent; nevertheless, at completion of induction, he demonstrated no further disease. His DI is being controlled with desmopressin.
References:
1.Ishigaki H, Hatta N, Yamada M, Orito H, Takehara K. Localised vulva Langerhans cell histiocytosis. Eur J Dermatol. 2004;14(6):412-414.
2.Haupt R, Minkov M, Astigarraga I, et al; Euro Histio Network. Langerhans cell histiocytosis (LCH): guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years. Pediatr Blood Cancer. 2013;60(2):175-184.
3.Minkov M, Grois N, McClain K, et al. Langerhans Cell Histiocytosis: Histiocyte Society Evaluation and Treatment Guidelines. Pittman, NJ: Histiocyte Society; 2009. http://www.histiocytesociety.org/document.doc?id=290. Accessed February 13, 2014.
4.Gadner H, Minkov M, Grois N, et al; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013;121(25):5006-5014.