Dermatology MCQ - Infiltrative and Neoplastic Disorders - Generalised eruptive histiocytosis

A 35-year-old man presents with a 6-month history of successive crops of dozens of firm, red-brown papules symmetrically distributed on his trunk, proximal extremities, and face. The lesions are all in the same stage of development and are asymptomatic. He is otherwise healthy. A biopsy of a papule reveals a dense dermal infiltrate of monomorphous histiocytes with abundant, pale cytoplasm. Immunohistochemical staining is positive for CD68 and negative for CD1a and S-100. Which of the following is the most accurate statement regarding this condition?

A. It is associated with a high risk of internal malignancy and requires an extensive oncologic workup.
B. It is a self-limited disorder of infancy that spontaneously regresses without treatment.
C. It is characterized by recurrent crops of lesions that may persist for years but often eventually regress spontaneously.
D. It is definitively treated with a short course of high-potency topical corticosteroids.
E. It is caused by a mutation in the BRAF gene, and targeted therapy is first-line.

Correct Answer: C. It is characterized by recurrent crops of lesions that may persist for years but often eventually regress spontaneously.

Answer and Explanation

The correct answer is C. This question describes the classic presentation of generalized eruptive histiocytosis (GEH). The key clues are the adult onset, the successive "crops" of numerous, monomorphous (all looking the same) red-brown papules on the trunk and proximal extremities, and the histology showing a non-Langerhans cell histiocytosis (CD68+, CD1a-, S-100-). GEH is known for its chronic, waxing-and-waning course, but a key feature is its potential for eventual spontaneous regression after a period of years, even after a long and protracted course.

Why the Other Options are Incorrect:

• A. It is associated with a high risk of internal malignancy...: This is incorrect. Unlike some paraneoplastic eruptions, GEH is not typically associated with internal malignancy. However, it is always prudent to have a low threshold for investigating general health in any adult with a new, widespread eruption.

• B. It is a self-limited disorder of infancy...: This description fits benign cephalic histiocytosis or many cases of juvenile xanthogranuloma, not GEH. GEH primarily affects adults.

• D. It is definitively treated with a short course of high-potency topical corticosteroids: Topical corticosteroids are generally ineffective for GEH, as the process is primarily dermal and widespread. Treatment is challenging and not always necessary, given the potential for spontaneous resolution.

• E. It is caused by a mutation in the BRAF gene...: Mutations in the BRAF gene are a hallmark of Langerhans cell histiocytosis (LCH) and some cases of Erdheim-Chester disease, not GEH. GEH belongs to the non-Langerhans cell histiocytosis group, which generally lacks BRAF mutations.

Additional High-Yield Information for Exams:

• Histopathology: The histology shows a relatively monomorphous, dense dermal infiltrate of histiocytes with abundant, pale, eosinophilic cytoplasm. The nuclei are oval or reniform. Crucially, it lacks the giant cells (especially Touton giant cells) seen in juvenile xanthogranuloma and the atypical grooved nuclei of Langerhans cells.

• Immunophenotype: The cells are CD68+, Factor XIIIa+, and CD163+ (markers of the monocyte/macrophage lineage). They are CD1a- and S-100-, which definitively rules out LCH.

• Differential Diagnosis: The main differential for multiple, widespread histiocytic papules in an adult includes:

  • Generalized Eruptive Histiocytosis (GEH): As described.

  • Xanthoma Disseminatum: Lesions often become xanthomatous (yellow) over time and have a strong predilection for flexures and mucous membranes; it can be associated with diabetes insipidus.

  • Multicentric Reticulohistiocytosis: Lesions are typically flesh-colored to brown, have a cobblestone appearance, and are associated with severe destructive arthritis.

  • Langerhans Cell Histiocytosis: Lesions are often crusted, scaly, or purpuric and are CD1a+.

• Prognosis: The prognosis for GEH is generally excellent. It is a benign, purely cutaneous condition. Despite its chronicity, it often undergoes spontaneous resolution after a period of activity that can last from months to many years.

• Management & Rationale:

  • Rationale: The goal is to confirm the diagnosis to provide reassurance and to manage the condition symptomatically, as no reliably effective treatment exists and spontaneous resolution is common.

  • First-line: Skin biopsy for diagnosis and reassurance. Given the potential for spontaneous regression, a period of observation is often the most appropriate initial step.

  • Treatment (if desired for cosmetic reasons or rapid clearance): There is no standard therapy. Various treatments with limited reported success include systemic corticosteroids, methotrexate, tetracyclines, and phototherapy (PUVA or NB-UVB). Due to the benign nature and self-resolving course, aggressive immunosuppressive therapies are generally avoided.