Hand-Schuller-Christian Syndrome

Synonym: Class I histiocytosis.

Hand-Schuller-Christian Syndrome is one variant of Langerhan's cell histiocytosis (LCH) which was previously known as Histiocytosis X.
Langerhan's cell histiocytosis covers a spectrum of disorders that have been separately classified in the past as:

• Eosinophilic granuloma (localised bony lesions, single or multiple)
• Hand-Schuller-Christian syndrome itself (multiple bony lesions affecting the skull, associated with proptosis and hypothalamic infiltration) and
• Letterer-Siwe disease (aggressive systemic variant with involvement of soft tissue only).¹

These categories are not exclusive and overlap with progression between types.

All are diseases of abnormal Langerhan's cell proliferation, probably due to defective immunoregulation. Although no longer believed to be a truly malignant condition (most cases appear to be self-limiting), LCH does sometimes behave aggressively and its response to chemotherapy places it within oncologists' practice.

Characterised by :

• Presence of clonal proliferation of Langerhans cell (monocytes lineage)
• Contain Birbeck's granule (tennis racket- shaped)
• Express surface antigens S100 and CD11 and 14 surface monoclonal antibodies
• Variable numbers of eosinophils, lymphocytes and giant cells.

• Hand-Schuller-Christian syndrome is usually a disease of childhood but may affect any age.^2,3
• Family clusters⁴ and twin concordance⁵ have been described.
• Incidence - very rare.

Hand-Schuller-Christian syndrome:

• Diffuse eruptions particularly on the scalp and in the ear canals (due to multiple bony skull lesions)
• Frequent bouts of otitis media, mastoiditis and URTI
• Diabetes insipidus (due to involvement of the posterior pituitary stalk of the hypothalamus)
• Exopthalmus.

Bony lesions elsewhere:

• Non-specific aches and pains
• Incidental finding on x-ray
• Spinal involvement (may cause collapse of vertebral body with compression of spinal cord)
• Pathological fractures
• Dental problems due to involvement of jaw bones.

Systemic involvement:

• Seborrhoeic dermatitis of scalp or nappy region
• Lymphadenopathy
• Hepatosplenomegaly
• Fever
• Weight loss or failure to thrive
• Anaemia, pancytopenia
• Symptoms/signs of other organ involvement. For example, cirrhosis (due to liver involvement), ataxia and dysarthria (due to CNS involvement).

Tissue biopsy, FBC, renal and liver function tests, coagulation studies, bone marrow aspirates, skeletal survey, chest X-ray and urine osmolality, hearing tests.

Stage I: single lytic bone lesion
Stage II: multiple lytic bone lesions
Stage IIIa: bone plus soft tissue lesion, often associated with diabetes insipidus or exopthalmos (ie classical Hand-Schuller-Christian syndrome)
Stage IIIb: soft tissue only, disseminated form.

Where a single system affected e.g. bone, lymphatics or skin use minimum intervention to stop progression of the lesion e.g. curettage or intralesional injection of steroids.

Where more than one system involved, combination chemotherapy including steroids and vinblastine or etoposide.

Management of progressive disease not responding to above: unclear, possible use of allogenic marrow transplantation (if match) or antithymocytic globulin, prednisolone and cyclosporin (where no donor).

• At least 50% spontaneous regression.
• In the past,aggressive chemotherapy may have contributed to morbidity and mortality, especially in the very young.
• Progressive disease has a 50-60% mortality rate.