•Hyperosmolar syndrome with hypernatremia and defective osmolar regulation can be life-threatening in patients with concomitant diabetes insipidus (severe dehydration and hyperosmolar coma)

8.2.8.2 Pulmonary Sequelae

• Opportunistic infection due to Pneumocystis jerovecii, Aspergillus, Pseudomonas, or other infectious agents

• Lung fibrosis in two-thirds of patients with LCH lung involvement or with chronic relapsing lung

8.2.8.3 Hepatic Sequelae

• Liver fibrosis and cirrhosis

8.2.8.4 Psychosocial Problems

• Neurocognitive abnormalities

• Psychomotor retardation

8.2.8.5 Secondary Tumor

Occurring mainly in irradiated locations of LCH patients, in the form of:

•Leukemia: AML, ALL

•Astrocytoma, medulloblastoma, meningioma

•Hepatoma

•Osteogenic sarcoma of the skull

•Carcinoma of the thyroid

8.2.9Special Clinical Presentations of LCH

The following three terms are rarely used any more:

8.2.9.1 Acute Disseminated LCH

(Formerly Abt–Letterer–Siwe Syndrome)

• Severely ill child with involvement of two or more organs

• Mostly acute disease with dysfunction of organs (lung, liver, bone marrow, central nervous system, CNS)

• Mostly in infants or children less than 2 years of age

• Unfavorable prognosis

8.2.9.2 Chronic-Disseminated or Multifocal LCH (Formerly Hand–Schüller–Christian Syndrome)

•Often chronic disease

•The majority are children more than 2 years of age

•Rarely organ dysfunction

•Mostly characterized by bone lesions in skull, pelvis and extremities

•Exophthalmos in children with orbital lesions of one or both sides

•Diabetes insipidus: frequently severe form, sometimes partial or transient form: ADH-deficit; in magnetic resonance imaging (MRI), hypodense lesions in the hypothalamic and pituitary region

•Occasionally growth retardation or retardation of sexual maturation caused by hormonal deficiency

8.2.9.3 Eosinophilic Granuloma

•Unifocal or multifocal lesions of bones, lymph nodes, or lungs

•In children with eosinophilic granuloma of the bone, usually a favorable outcome

•Peak incidence between 5 and 10 years; occurs also in adolescents and adults

•Often as symptomatic disease, with coincidental diagnosis on radiological examination

•Systemic spread occurs rarely and within the first 6 months after first manifestation

•On X-rays, the lesions are characterized by a punched-out appearance, without sclerosis or periosteal reactions of the bone

•Occasionally pathological fracture of lesions in the long bones may occur (differential diagnosis: chronic osteomyelitis)

•Lesions in the vertebral bones may collapse, with adverse neurological or orthopedic consequences

Percentage of bone lesions of eosinophilic granuloma

8.3 Infection-Associated Hemophagocytic

Syndrome (IAHS)

•Similar pathology, clinical manifestation, and laboratory diagnosis to familial erythrophagocytic lymphohistiocytosis (FEL see 8.4 or primary or inherited hemophagocytic lymphohistiocytosis, HLH)

–Secondary HLH triggered by infection (e.g. EBV), autoimmune, metabolic, or malignant disorders

–Also sometimes referred to as Macrophage Activation Syndrome (MAS)

–Treatment usually requires therapy for the underlying condition as well as for the HLH component; treatments for reactive or secondary HLH include steroids, etoposide and cyclosporin as well as intravenous gammaglobulin and steroids, Campath (anti-CD52 monoclonal antibody), IL1 Receptor antagonists, and TNF inhibitors