8.2.5Differential Diagnosis

Other forms of histiocytosis; reactive histiocytosis with dysfunction of various organs: in chronic infections (e.g., tuberculosis, atypical mycobacterial infection, toxoplasmo- sis, cytomegalovirus infection), rheumatoid disorders, sarcoidosis, autoimmune disorders, storage diseases (e.g., silicosis, asbestosis, hemosiderosis), chronic granulomatous disease

•Severe combined immune deficiency (SCID)

8.2.6Prognosis

•Initial response to therapy, i.e., during the first 6–12 weeks of therapy, is a key prognostic factor.

•Other prognostic factors that may adversely influence outcome include:

– Age at diagnosis, less than 2 years, especially if less than 6 months of age

– Number of involved organs: the higher the number of organ systems involved, the less favorable the prognosis

– Presence of organ dysfunction, especially of lung, liver, or bone marrow infiltration

– Extensive skin involvement (with exception of infants with isolated skin involvement)

8.2.7General Therapeutic Approach

8.2.7.1 Surgery

•Biopsy for diagnostic evaluation

•In patients with isolated bone involvement, curettage if accessible and not likely to result in an adverse outcome; injection of steroids into lesions can also induce their regression

8.2.7.2Radiotherapy

•Where there is unifocal involvement and risk of sequelae (e.g., risk of vertebral bone collapse with neurological sequelae)

•Dose of 7–10 Gy is usually sufficient

•Irradiation is indicated in the following locations and/or with high risk of sequelae:

– Orbit

–Mastoid

–Vertebrae

–Base of skull

–Ulceration of skin

–Untreatable pain

–Pathological fracture with prolonged recovery

8.2.7.3 Chemotherapy

•Indicated in disseminated multifocal manifestation

•Active substances: vincristine, vinblastine, prednisone, etoposide, cyclophosph- amide, doxorubicin, procarbazine, 2-chlorodeoxyadenosine; of note etoposide, cyclophosphamide, doxorubicin, and procarbazine are not currently used routinely

•Maintenance treatment is recommended to include 3 weekly treatment with vin- blastine and 5 days of steroids; in some patients with high-risk or slowly respond- ing disease, oral 6-mercaptopurine and methotrexate are given in conjunction with vinblastine and steroids, although no definitive study has proven this combination is better than vinblastine or steroids alone

•Duration of treatment: 6–12 months; some patients with multiple relapses need long-term treatment; 12 months of maintenance therapy has been shown in the randomized LCH III trial to significantly reduce the number of disease recurrences compared to 6 months of maintenance therapy

8.2.7.4Stem Cell Transplantation

•In high-risk patients, e.g. disseminated form, or in patients who do not respond to conventional treatment

•In patients with life-threatening relapse that is nonresponsive to systemic therapy

8.2.8Long-Term Sequelae

•Occasionally long-term chronic active disorder in patients with generalized LCH including skeletal involvement,

•Long-term sequelae occur in endocrine, pulmonary, skeletal, orthopedic, hepatic, hearing loss, neurological, neuropsychiatric systems or as secondary malignant disorders

8.2.8.1 Endocrine Sequelae

•Diabetes insipidus in 5–30%

•Growth retardation and short stature: often concomitant with diabetes insipidus and together with delay or absence of puberty; part of the hypopituitarism that accompanies pituitary involvement in approximately 60% of patients with DI

•Hyperprolactinemia with or without galactorrhea

•Hypogonadism: in approx. 4% of patients

•Panhypopituitarism

•Hypothyroidism