Dermatology Online Journal

Perifollicular Langerhans cell histiocytosis
Adnan Mir MD PhD, Max Fisher MD, Hideko Kamino MD, Nicholas A Soter MD
Dermatology Online Journal 18 (12): 6

The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York

---

Abstract

A 25-year-old man presented with a 13-year history of an erythematous, papular eruption of his face and trunk, which was treated in the past as acne and psoriasis with isotretinoin and methotrexate, respectively. Histopathologic examination demonstrated an infiltrate of Langerhans cells, which was consistent with Langerhans cell histiocytosis. The epidemiology, clinical presentation, and treatment options of this disease are reviewed.

---

History

Figure 1	Figure 2

Figure 3	Figure 4

A 25-year-old man from Pakistan was referred to the Charles C. Harris Skin and Cancer Pavilion for evaluation and treatment of a longstanding, asymptomatic eruption of the face, ears, chest, and back. He developed the eruption at the age of 13 years and had been treated in Pakistan with isotretinoin for presumed acne vulgaris and with methotrexate for presumed psoriasis. Each of these medications yielded some benefit, but he has never been clear. He has never had lesions on his extremities. At the time of presentation, he had been on methotrexate for three years. Upon discontinuation pending a definitive diagnosis, his condition slowly began to worsen. He denied any systemic complaints, relevant past medical history, pertinent family history, and the use of medications prior to onset.

Physical examination

On the forehead and cheeks were erythematous papules that coalesced into plaques. Scattered, erythematous papules were present on the nose, chin, chest, and upper back in an acneiform pattern. The external ear canals also were affected. The axillae showed minimal active disease but had appreciable scars. The fingernails showed onychorrhexis and onycholysis, with minor pterygium and slight nailbed scars. No cervical, axillary, or inguinal lymphadenopathy was noted. Although there were no oral lesions, there was some gingival recession.

Laboratory data

A comprehensive metabolic panel, complete blood count, activated partial thromboplastin time, C-reactive protein, erythrocyte sedimentation rate, parathyroid hormone, calcium, cortisol, thyroid function tests, human growth hormone, and serum protein electrophoresis were normal. A chest radiograph was normal.

Histopathology

Figure 5

There is a nodular, perifollicular infiltrate of large mononuclear cells with abundant amphophilic cytoplasm and large vesicular nuclei. Some nuclei have a kidney-shaped appearance, and others have a longitudinal groove. There are several, multinucleated cells. There are a few lymphocytes, neutrophils, and eosinophils. Immunohistochemical stains for CD1a and, to a lesser degree, S-100 protein are positive in the neoplastic cells.

Discussion

Langerhans cell histiocytosis (LCH), which is disorder of proliferation of the Langerhans cell, the primary antigen presenting cell in the skin, initially was described in the early twentieth century as Letterer-Siwe disease, Hand-Schüller-Christian disease, and eosinophilic granuloma. The three entities were recognized as related and placed under the umbrella of Histiocytosis-X in the 1950s. The name Langerhans cell histiocytosis subsequently was adopted in 1989 when Langerhans cells were identified as essential for the diagnosis. LCH is primarily found in children, with an annual incidence in children overall of five per million and from five to 14 years of age of one per million. The incidence in adults is approximately the same as it is in older children. The male-to-female ratio is 2:1 in children and is slightly higher in adult women than it is men [1, 2, 3].

Childhood disease has various presentations that range from single-system, limited disease to severe, multi-organ disease with high mortality. Bone is most frequently involved, followed by skin [3]. Other organs that may be involved include the hypothalamic-pituitary axis, orbits, gastrointestinal tract, lungs, liver, spleen, and lymph nodes. Prognosis is related to age of onset, single- versus multi-system disease, and evidence of organ dysfunction. The best prognostic factor is response to chemotherapy [4]. Disease isolated to the skin accounts for only 10 percent of all cases. In children, the most common form of skin involvement consists of small, red and yellow papules on the scalp and retroauricular and intertriginous areas. It also can present with solitary nodules or oral lesions. Although the pattern of skin disease is not predictive of systemic involvement, it has been reported that nail involvement is a strong marker for systemic disease [5].

In adult-onset, single-organ disease, bones or lungs are most often the affected organs. However, most adults affected with lung-only disease are smokers and it is thought to be a reactive process. Other possible involved organs in adults are similar to those involved in children, although adults are more likely to have thyroid involvement and less likely to have gastrointestinal tract and lymph node involvement. Skin is frequently involved in multi-organ disease and usually exhibits an acneiform eruption, xanthomatous lesions, or erosive intertrigo [2, 6].

As with the patient presented in this report, individuals may present with one form of LCH, which may evolve into another form. Although there is no documentation of his initial presentation, it is clear from his axillary scars that he has had erosive intertrigo and that he is currently affected by a more acneiform pattern.

The pathophysiology of LCH has not yet been determined. There is controversy even about whether it is a neoplastic or a reactive process. The reality is likely that some forms are reactive and others are neoplastic. Early research suggested a link between HHV-6 infection and LCH, but recent reports have challenged this assertion [7].

Treatment of LCH depends on age, extent of disease, and risk factors. For patients with disease localized to the skin, topical glucocorticoids, phototherapy, and topical nitrogen mustard are the preferred treatments [4, 6]. Excimer laser, PUVA photochemotherapy, and systemic retinoids also have been used with varying levels of success [8, 9, 10]. In more advanced disease, treatment may include combinations of systemic glucocorticoids with vinblastine, etoposide, mercaptopurine, and methotrexate. The Histiocyte Society has recommended specific treatment ladders based on age, number of systems involved, and presence of organ dysfunction [11].

Our patient’s presentation is unique because his disease began as a child, but a diagnosis was not made until adulthood. It is possible that with aggressive treatment upon his initial presentation, he may have had a prolonged remission. He is currently being evaluated for systemic involvement. Without any systemic features, he would likely respond favorably to phototherapy and topical glucocorticoids.

References

1. Drutz JE. Histiocytosis. Pediatr Rev 2011; 32: 218 [PubMed]

2. Arico M, et al. Familial clustering of Langerhans cell histiocytosis. Br J Haematol 1999; 107:883 [PubMed]

3. Alston RD, et al. Incidence and survival of childhood Langerhans cell histiocytosis in Northwest England from 1954 to 1998. Pediatr Blood Cancer 2007; 45: 555 [PubMed]

4. Satter EK, High WA. Langerhans cell histiocytosis: a review of the current recommendations of the Histiocyte Society. Pediatr Dermatol 2008; 25: 291 [PubMed]

5. Jain S, et al. Nail changes in Langerhans cell histiocytosis. J Eur Acad Dermatol Venereol 2000; 14: 212. [PubMed]

6. Tatevossian R, et al. Adults with LCH — orphans with an orphan disease. Clin Med 2006; 6: 404 [PubMed]

7. Glotzbecker MP, et al. Langerhans cell histiocytosis and human herpes virus 6 (HHV-6), and analysis by real-time polymerase chain reaction. J Orthop Res 2006; 24: 313 [PubMed]

8. Cardoso JC, et al. Langerhans cell histiocytosis in an adult: good response of cutaneous lesions to acitretin. Clin Exp Dermatol 2010; 35: 627 [PubMed]

9. Sakai H, et al. Satisfactory remission achieved by PUVA therapy in Langerhans cell histiocytosis in an elderly patient. J Dermatol 1996; 23: 42 [PubMed]

10. Vogel CA, et al. Excimer laser as adjuvant therapy for adult cutaneous Langerhans cell histiocytosis. Arch Dermatol 2008; 144: 1287 [PubMed]

11. Gadner H, et al. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood 2008; 111: 2556 [PubMed]

© 2012 Dermatology Online Journal