Asymptomatic Papular Eruption in a 60 Year Old Man.

A 60-year-old man presented with asymptomatic, bilaterally symmetrical gradually progressive, generalized papular eruption since 3 months. Few lesions had spontaneously regressed, while others persisted. There was no history of insect bite reaction, viral fever, drug intake prior to onset of lesions.

Examination revealed bilaterally symmetrical discrete skin colored papules ranging from 2 to 4 mm in diameter over upper [Figure 1a] and lower limbs [Figure 1b]. The palms, soles, and mucosae were spared. General physical examination revealed no abnormality.

Figure 1

(a) Multiple skin colored papules over both forearms (b) Discrete papules over inner aspect of arm (c) Discrete papules over inner aspect of thigh

Routine blood investigations including lipid profile were within normal limits. Histopathology from papule over forearm revealed histiocyte-like cells, irregularly grouped in upper and middermis. The cells had pale cytoplasm with oval nuclei [Figure 2a]. An immunohistochemistry showed that the histiocyte-like cells expressed CD 68 and were negative for S100 and CD1a [Figure 2b].

Figure 2

(a) Irregularly grouped histiocytes in upper and middermis (b) Immunohistochemistry demonstrating CD68 positivity

Question

What is your diagnosis?

Diagnosis

Generalized eruptive histiocytosis(GEH).

Differential Diagnosis

Differential Diagnosis that can be kept are: Papular PR, Eruptive xanthoma, Eruptive Histiocytosis, Granuloma Annulare.

Discussion

Histiocytoses are a broad enigmatic group of different and partially related disorders, characterized by the accumulation of reactive or neoplastic histiocytes in various tissues. They are broadly classified as Langerhans and non-Langerhans cell histiocytosis (NLCH).

GEH is a rare variant of NLCH, which is characterized by recurrent crops of small skin colored papules on the proximal extremities and occasionally the trunk, affecting mainly adults. In 1963, Winkelmann and Muller reported three cases of a generalized benign papular histiocytic reticulohistiocytosis of adulthood, which they aptly called generalized eruptive histiocytoma.[1]

GEH usually follows a benign course, occasionally leaving behind hyperpigmented macules during remission. Rare cases of atypical GEH with erythematous papules and plaques have been reported in patients with hematopoietic malignancy, such as acute myelomonocytic leukemia and chronic myelomonocytic leukemia during blast crises.[2]

Histopathology from lesions of GEH reveals an infiltrate composed of monomorphic histiocytic cells in the upper and mid dermis. Ultrastructural studies show that these cells lack birbeck granules but contain occasional concentric laminated bodies. Immunohistochemistry demonstrates positive staining for CD68 lysosyme, alpha1 antitrypsin, HAM-56, CD11b, CD14b, Mac387, and factor XIIIa.[3] The spontaneous regression of GEH may be mediated by massive apoptotic cell death as indicated by the ultrastructural findings of chromatic margination, nuclear condensation, cytoplasmic vacuolization, and fragmentation.[4]

GEH mimics benign cephalic histiocytoses (BCH), juvenile xanthogranuloma (JXG), papular xanthoma, and xanthoma disseminatum. While BCH occurs in children, the others may be easily excluded in view of the color of the lesions and the presence of both foamy cells and Touton giant cells. Multicentric reticulohistiocytosis is ruled out because of the absence of arthritis and the lack of giant cells with ground-glass cytoplasm.[3] Other diseases, such as sarcoidosis, urticaria pigmentosa, lymphoma, and xanthomata, may represent a problem in differential diagnosis only from a clinical point of view.[5]

There are no known specific treatments for GEH; however, Psoralen + UVA (PUVA) therapy and recently isotretinoin has been tried with some success.[3]

Our patient has been on a regular follow-up for over 6 months. Few lesions have regressed with time, while remaining lesions are persistent. NLCH are a confusing array of disorders. Until 2010, only 50 cases of GEH in adults and nine cases in children had been reported.[6] It is a rare disease which necessitates immunohistochemistry and ultra structural studies over and above routine histopathology to appropriately manage the patients.

Learning points

NLCH is a spectrum of disorders. GEH is a rare variant of NLCH. The generalized distribution of asymptomatic papules with histopathological evidence of histiocytic infiltration in the dermis and CD68 positivity on immunohistochemistry are hallmarks of Generalized Eruptive Histiocytosis (GEH).