Histiocytosis X/Langerhans Cell Histiocytose
Saturday, January 01, 2011
Langerhans cell histiocytoses (Class I histiocytosis) are a
group of disorders most common in childhood due to the accumulation
or proliferation of a clonal population of cells bearing the
phenotype of a Langerhans cell that has been arrested at an early
stage of activation and is functionally deficient. This disorder is
classified as single-system disease, multisystem disease, or
multisystem disease with organ dysfunction. The skin is one of the
most frequently affected organs in patients with both localized
(skin only) and multisystem disease. The course in any patient
varies from benign (usually associated with localized disease or
multisystem disease without organ dysfunction) to severe and fatal,
with internal organ dysfunction. Dysfunction of lungs, liver,
and/or bone marrow are very poor prognostic signs. Skin-limited
cases and sometimes systemic disease may spontaneously involute
without therapy. Disease may recur after involution, even years
later; therefore long-term follow-up is essential. Langerhans cell
histiocytoses syndromes are uncommon, and most patients should be
evaluated and usually managed at tertiary referral centers.
A staging system accurately determines which patients require
and benefit from chemotherapy. Therapy is individualized to the
patient's extent of disease and its effect on organ systems.
Needless chemotherapy-induced morbidity should be avoided, with no
or only local therapy for local disease. A biopsy of affected
tissue for diagnoses should be performed. Evaluation for internal
organ involvement is required in all patients to accurately stage
them and determine appropriate treatment. Staging evaluation
includes bone radiographs (skeletal survey), CBC with platelets,
liver function tests including PT/PTT, chest radiograph,
liver-spleen scan (if liver function testing is abnormal), bone
marrow biopsy (if the CBC is abnormal), and urinalysis, serum
electrolytes, perhaps water deprivation testing, and computed
tomography of the brain (to look for diabetes insipidus). The
discussion below is limited to the treatment of skin disease.
Multisystem disease must be managed with the guidance of an
experienced oncologist, preferably at a tertiary referral
Patients may be observed without therapy. Autoinvolution often
- For a solitary lesion, excision may be curative.
- Topical nitrogen mustard 20 mg/100 mL tap water applied once
daily until the lesions clear (several weeks). Weekly or biweekly
maintenance therapy may be required.
- For patients who have failed treatment with nitrogen mustard,
systemic PUVA twice weekly is recommended. Maintenance may be
- Prednisone alone, up to 2 mg/kg in children, may be used for
extensive, unresponsive cutaneous disease.
- Trimethoprim/sulphamethoxazole 12-15 mg/kg/day for 1-3 months
may be effective in children.
- Thalidomide 100 mg/day for 1 month, then 50 mg/day for 1-2
- Isotretinoin 1.5 mg/kg/day for 6 or more months may induce a
- For severe skin-limited disease, single agent chemotherapy may
be considered. Effective agents have included methotrexate,
vinblastine, 6-mercaptopurine, and etoposide. Alpha interferon in
doses of up to 6 million units daily can be used in refractory
disease. While cyclosporine in high doses 12 mg/kg/day leads to
resolution of skin disease, relapses frequently occur.
- Congenital self-healing reticulohistiocytosis is a benign
Langerhans cell histiocytosis. This diagnosis should be entertained
in neonates with lesions over 1 cm and skin involvement only. As
the name implies, autoinvolution occurs universally by 3
- Severe combined immunodeficiency syndrome and graft vs. host
disease may closely mimic Langerhans cell histiocytosis. In
Langerhans cell histiocytosis, most patients are immunologically
normal prior to therapy when evaluated by standard tests.
- Morbidity and mortality may be reduced by appropriate
nonaggressive therapy (often no therapy). Do not produce
unnecessary permanent sequelae from overaggressive local or
- Long-term follow-up is essential to detect disease relapse and
to monitor for long-term complications (cosmetic, orthopaedic,
hearing impairment, loss of permanent teeth, pulmonary fibrosis,
cor pulmonale, portal hypertension, cirrhosis, endocrinologic
disorders from pituitary involvement, and second