Histiocytosis
also Complications of chemo: general

• Diverse group of disorders
• Prominent proliferation/accumulation of cells of the monocyte-macrophage system of BM origin
• Think about histiocytosis whenever malignancy, bony pain or rash is in the differential or the patient has constitutional symptoms or bone marrow suppression (cell lines down), or diabetes insipidus, persistent diaper rash
• Often have severe bone pain out of proportion to physical exam
• it's one of the 3 classic nonosseous tumors that we must consider in evaluation of bone pain, along with Neuroblastoma and Leukemia
• There are 3 classes based on histopathologic findings.

1. LCH (EHL) Dave 'Birbeck' on CD1a: bone pain, rash, draining ear, draining pee, bumps, pallor/bleed, pulmonary infiltrates
2. HLH-APC-FEP-IAHS
3. malignant

Class I- Langerhan Cell Histiocytosis

• clonal proliferation of cells of monocyte lineage containing characteristic Birbeck granules and are CD1a positive; Langerhans cell = antigen presenting cell of the skin
• 3 types (alphabetic - the later, the more spread)
  • Eosinophilic granuloma - localized
  • Hans-Schuller-Christian - limited spread
  • Letterer Siwe- disseminated
• Multisystem involvement:
• Skeletal (80%): osteolytic lesions (asx or painful w/ local swelling), pathologic fx's, skull commonly affected, can get spinal compression fx
• Skin (50%): seborrheic dermatits of scalp or diaper area, petechiae or hemorrhagic rash
• chronically draining otitis media
• bilateral exophthalmos
• diabetes insipidus
• pulmonary infitrates on CXR (10-15%)
• bumps: lymphadenopathy (33%),  hepatosplenomegaly (20%)
• may have systemic manifestations: fever, wt loss, malaise, FTT
• BM involvement: anemia, thrombocytopenia
• hepatic or CNS involvement
• Dx: Tissue biopsy, CBC, LFT's, coags, skeletal survey, CXR, urine osmolality
• Treatment: observation, chemo, immunosuppressives and BMT
• Px: good for single system disease - high chance of spontaneous remission; worse for multisystem disease

Class II- Hemophagocytic LymphoHistiocytosis (HLH)

• clonal proliferation of antigen-presenting cells
• 2 forms: similar presentation: fever, wt loss, irritability
  • FEL- autosomal recessive; Familial erythrophagocytic lymphohistiocytosis: characterized by severe immunodeficiency, almost always fatal, and always Dx'd <4 years old
  • IA-HS- Infection-associated hemophagocytic syndrome; may be Dx'd in older pts and has much better prognosis if infection is treated appropriately
• Diagnostic criteria (need all 5):
  • Fever
  • splenomegaly
  • cytopenias (2 cell lines down)
  • hyperlipidemia or hypofibrinogenemia
  • tissue biopsy (hemosiderin-laden macrophages)
• Treatment/Prognosis:
  • FEL: Nearly uniformly fatal
    • Chemotherapy (etoposide), immunosupressive therapy
    • BMT
  • IAHS: Good prognosis if infectious agent can be identified and treated, poor if not

Class III- Malignant form - true malignancy of monocyte-macrophage lineage

Now, it is important to note that this class of disease is rare, but should be kept in the back of our minds when we see a painful bony lesion (it's one of the 3 classic nonosseous tumors that we must consider in evaluation of bone pain, along with Neuroblastoma and Leukemia) or chronic constitutional symptoms like weight loss, irritability, fatigue.....

Also see Wiscott Aldritch, other skin stuff