Symptoms and physical exam will depend on organ involvement at the time of presentation. 

The rash is the most common presentation. In children, the rash may be misdiagnosed as seborrhea or atopic dermatitis but will not respond to typical treatment for these disorders. The rash of LCH ranges from a single lesion to widespread involvement. Characteristics include scaly papules, nodules, or plaques and can resemble seborrheic dermatitis. One may distinguish LCH by the presence of petechiae, bloody crusting, or firmly indurated nodules.

Bony involvement occurs in about 78% of patients. Solitary osseous lesions are usually incidentally found and may include the skull, hip/pelvis, femur, or ribs. This bony involvement may present incidentally, when obtaining imaging for another complaint, or may produce bone pain. 

Pulmonary lesions occur in 20% of patients, and lymph node involvement in 30%. As such, the patient may present with pulmonary symptoms or lymphadenopathy. Hepatosplenomegaly may be present as well. 

Langerhans cell histiocytosis also has a predilection for infiltration of the pituitary and causing diabetes insipidus. If this is the initial presentation, the patient may have polyuria, polydipsia, dilute urine, and hypernatremia. 

Biopsy of the involved site (usually skin) is required to confirm the diagnosis. Lesions will stain positive for S-100 and CD-1a. Cytoplasmic Birbeck granules will be present on electron microscopy. When the diagnosis is confirmed, workup for systemic involvement should include a skeletal survey, abdominal ultrasound, complete blood count (with bone marrow biopsy if indication of bone marrow involvement), and evaluation for diabetes insipidus. [8][9][10][9]

CT scanning or MRI

Both CT scan and MRI are invaluable for assessing the hypothalamic-pituitary area. Fluorodeoxyglucose (FDG) PET scanning also is being used to assess patients with LCH. The technique is far more sensitive than bone scan for early detection of disease in the spleen, lymph nodes, and lung. In fact, FDG PET scan is now also being routinely used to monitor disease during treatment.

Other Tests

• Pulmonary function testing may help identify asymptomatic patients with lung involvement

• Small bowel series is recommended in patients with failure to thrive, diarrhea, and malabsorption

• Neurological and visual testing

• Auditory testing

• Recent studies suggest that CSF fluid can be used to detect biomarkers like glial fibrillary acidic protein to evaluate the onset of disease and response to therapy.

• Skin biopsy can establish the diagnosis[11][12]

Treatment varies greatly depending on the involved organs. If the disease is isolated, observation alone may be appropriate. Surgical removal of an isolated area is also a treatment option. Isolated skin lesions may resolve on their own, especially if they present in infancy (congenital self-healing reticulohistiocytosis), or may be treated with topical steroids, oral methotrexate, or thalidomide. Chemotherapy and radiation may be used for more systemic involved cases. There are several different chemotherapy protocols that have been used; currently, protocols are using prednisone and vinblastine, though other regimen options include vincristine, cytosine arabinoside, prednisone, cladribine, or pamidronate. [13]

Late complications are common; therefore, follow up with oncology is crucial. Complications include diabetes insipidus, growth failure, delayed puberty, tooth loss, mandibular bone loss, hearing loss, secondary cancers, neurologic/cerebellar effects, liver disease, and pulmonary fibrosis. 

• Acrodermatitis enteriropathica

• Acropustulosis of infants

• Congenital candidiasis

• Eosinophilic pustular folliculitis

• Incontinentia pigmenti

• Leukaemia

• Lymphoma

• Mastocytosis

• Myeloma

• Neonatal pustular melanosis

More than 50% of children under the age of 2 with disseminated Langerhans cell histiocytosis will die of the disease, but those with localized disease may have a prolonged life-span. For those who have been treated and do not have more lesions at 12 to 24 months, a full recovery can be expected. When there is lung involvement, the prognosis is not good. However, patients with isolated skin involvement and a solitary lymph node involvement tend to have a good prognosis.

Unfortunately, nearly 50% of patients with Langerhans cell histiocytosis are prone to a variety of complications which include the following:

• Musculoskeletal disability

• Skin scarring

• Diabetes insipidus

• Hearing impairment

• Neuropsychiatric problems like depression, anxiety, and intellectual impairment

• Pulmonary impairment

• Secondary malignancies like lymphoblastic leukemia and sodi tumors

• Growth retardation

• Liver cirrhosis

Prognosis depends on whether the initial presentation was a low-risk disease (isolated to the skin, lymph nodes, or pituitary gland) or high-risk disease (involving the spleen, liver, bone marrow, lung, or skeleton). Mortality may be low for isolated lesions (< 5%) and as high as 50% for the more widespread disease. 

The management of LCH is with an interprofessional team that includes oncology nurses. The key is to make an early diagnosis.Healthcare workers need to be aware that the rash is the most common presentation. In children, the rash may be misdiagnosed as seborrhea or atopic dermatitis but will not respond to typical treatment for these disorders. The rash of LCH ranges from a single lesion to widespread involvement. Characteristics include scaly papules, nodules, or plaques and can resemble seborrheic dermatitis. One may distinguish LCH by the presence of petechiae, bloody crusting, or firmly indurated nodules.

The outcomes of LCH depend on its presentation. Those with disseminated disease will die within 24-48 months. Those with localized disease do have a better prognosis but the quality of life is reduced.