6-month-old presents with scalp, groin and truncal rash

Case discussion

The correct answer is B, Langerhans cell histiocytosis (LCH), a proliferative disorder involving Langerhans cells which can infiltrate multiple organ systems, most commonly the skin and bones. Its pathogenesis is not well understood, and it is unclear whether LCH represents a neoplastic or reactive process. Mutations in BRAF-V600E are thought to play a role. The clinical course varies as there is a broad spectrum of disease, ranging from single-organ disease to severe multisystem disease. It can present at birth or within the first few months of life. The peak incidence is between ages 1 and 4 years. Children younger than 1 year are usually more severely affected.

LCH most commonly presents as a rash comprised of red-brown scaly papules, often with secondary findings such as erosions, crusting or hemorrhage. Petechial and purpuric lesions may also occur. The rash classically presents in a seborrheic dermatitis-like distribution involving the scalp, postauricular areas and flexural areas including the axillae and inguinal folds. The rash is usually asymptomatic. While seborrheic dermatitis, inverse psoriasis and atopic dermatitis can also involve the scalp and intertriginous areas, the failure to respond to conventional therapy for inflammatory dermatoses is an important clue that should prompt consideration for LCH. Less common cutaneous manifestations of LCH, especially in neonates, include vesiculopustular eruptions, nodules, ulcers or a “blueberry muffin” rash mimicking extramedullary hematopoiesis.

Many infants with cutaneous LCH will also have extra-cutaneous manifestations. Oral findings may include ulcers, gingival hemorrhage and loosening of the teeth. Bony involvement can manifest as asymptomatic lytic lesions, deformation and fractures, with the skull being the most common site affected. Patients with bony involvement may present with pain and/or swelling of the affected area. Lymphadenopathy may also occur, most often involving the cervical chain. Endocrine involvement is usually in the form of diabetes insipidus which manifests as polyuria and polydipsia. Hepatosplenic involvement can be severe and includes liver fibrosis and dysfunction. Pulmonary, gastrointestinal and central nervous system involvement may also occur. Bone marrow infiltration can result in pancytopenia. Patients with multi-organ involvement often also present with systemic symptoms such as fever and weight loss.

When LCH is suspected clinically, a skin biopsy and immunohistochemistry will confirm the diagnosis. Histopathology findings include a diffuse infiltrate of S100 and CD1a-positive histiocytes with characteristic eccentric reniform nuclei. Once the diagnosis of LCH is confirmed via histopathology, this should prompt workup to evaluate for systemic involvement. Laboratory workup should include a complete blood count with differential, complete metabolic panel, coagulation studies and urine osmolality. Imaging modalities such as a chest X-ray and a complete skeletal survey should be performed to evaluate for the presence of lung and bony involvement, respectively. An abdominal ultrasound to evaluate for hepatosplenomegaly may also be indicated. Additional workup including a bone marrow biopsy and MRI studies may be needed to evaluate for other internal organ involvement.

The treatment and prognosis of LCH depends on the extent of organ involvement. Most infants with skin-limited disease will experience self-resolution of skin lesions over time, with an overall favorable prognosis. Topical therapies tend to be ineffective. Although less common, skin-limited disease may later progress to involve internal organs years after resolution of skin findings, thus long-term follow up is recommended. Multi-organ disease may require chemotherapy and generally portends a poorer prognosis. Multi-disciplinary care is needed with oncology and other appropriate specialists. All patients with LCH require long-term follow up to evaluate for reactivation or late sequelae.

References:

Dhar S, et al. Pediatr Dermatol. 2020;doi:10.1111/pde.14389.

Eichenfield LF, et al. Neonatal and infant dermatology. 3rd ed. London: Elsevier; 2015.

Paller A, Mancini AJ. Hurwitz clinical pediatric dermatology: A textbook of skin disorders of childhood and adolescence. 5th ed. Edinburgh: Elsevier; 2016: 557-572.

Satter EK, et al. Pediatr Dermatol. 2008;doi:10.1111/j.1525-1470.2008.00669.x.

For more information:

Michele Khurana, MD, is an attending physician at Children’s Hospital of Philadelphia. She can be reached at khuranam@email.chop.edu.