Complications

Complication
Timeframe
Likelihood
short term
low

Usually happens early in the disease course and is due to chronic progressive liver damage.

Liver transplant may be the only curative procedure.[125]

Cirrhosis

short term
low

Usually happens early in the disease course and is due to chronic progressive liver damage.

Liver transplant may be the only curative procedure.[125]

Primary sclerosing cholangitis

long term
low

Occurs in 3% to 16% of patients, due to mastoid bone lesions.[126]

Hearing loss is often conductive, but damage to the inner ear can cause sensorineural hearing loss.[49]

Evaluation of hearing loss

long term
low

May occur in patients with skin involvement. Rarely evolves into juvenile xanthogranuloma.

long term
low

Solid tumors such as neuroblastoma and retinoblastoma, acute myelogenous leukemia, and acute lymphoblastic leukemia have all been reported during or after treatment.[127]

Hodgkin and non-Hodgkin lymphomas are more frequently reported among adults, with only a few cases reported in children.[128]

long term
low

May occur up to 20 years after diagnosis either from end-organ failure or from treatment-induced complications such as secondary malignancies.

variable
medium

Occurs in 7% to 20% of patients.[27] Can either precede or manifest after diagnosis. Symptoms of polydipsia and polyuria should be investigated, even if they occur many years after the diagnosis of LCH.[2]

Risk factors include the presence of multisystem disease and the involvement of craniofacial bones, especially the orbit and skull base.[27] Intensive chemotherapy given at the onset of diagnosis may reduce the risk of developing this condition.

There are case reports of the chemotherapeutic agent cladribine being used to reverse the condition, but it is usually considered irreversible.[120]

Diabetes insipidus

variable
medium

Patients are at increased risk of growth hormone deficiency (10% of patients), delayed puberty, and panhypopituitarism.[2] Measurement of weight and height, and assessment of Tanner pubertal stage, is recommended every 6 to 12 months until the child has finished growing.[2] Growth hormone replacement is indicated for growth hormone deficiency.[121]

Hypopituitarism

variable
medium

Occurs due to a combination of factors including growth hormone deficiency, bony involvement, chronic corticosteroid therapy, and the effects of chronic disease itself, all resulting in a compromised final height.[121][122] Treatment depends on the etiology.

Evaluation of short stature

variable
medium

Occurs in 42% of long-term survivors.[44] May be due to the disease itself (bone involvement) or the treatment.

Growth cessation, pathologic fractures, and scoliosis have all been reported. Less common manifestations include residual proptosis, loss of teeth, and asymmetric jaw growth.[44]

variable
medium

Occurs in patients with lung involvement, predominantly in adolescents and adults, particularly smokers.[23] There is a known association between lung involvement and lung cancer in patients who smoke.[123]

Cessation of smoking may stop progression of the disease.[115]

variable
low

Occurs in up to 4% of patients and is potentially life-threatening.[3][36]

Manifests as cerebellar symptoms, seizures, focal neurologic deficits, cognitive impairment, or changes in behavior. Can occur several years after diagnosis or, less frequently, at the initial presentation. Cognitive impairment has been reported in up to 40% of long-term survivors of multisystem disease.[124]

Risk factors include the presence of diabetes insipidus or CNS-risk bone lesions (i.e., lesions of the orbit, mastoid, or temporal bone).[3][36]

All patients should have a brain magnetic resonance image annually after ceasing therapy, to detect early CNS radiographic degeneration.

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