eMedicine Specialties > Dermatology > Malignant Neoplasms

Langerhans Cell Histiocytosis: Treatment & Medication

Author: Christopher R Shea, MD, Professor and Chief, Section of Dermatology, Department of Medicine, University of Chicago
Coauthor(s): Markus D Boos, PhD, Medical Scientist Training Program, Pritzker School of Medicine, University of Chicago
Contributor Information and Disclosures

Updated: Aug 26, 2009

Treatment

Medical Care

The choice of therapeutic regimen is based on disease severity. The International LCH Study of the Histiocyte Society proposes the stratification of Langerhans cell histiocytosis (LCH) cases by the number of systems involved. They further categorize those cases with single-system involvement by the number of sites within that system (eg, monostotic vs polyostotic bone disease, solitary vs multiple lymph node involvement). In addition, the presence or the absence of organ dysfunction is used to stratify patients with multisystemic disease; the presence of any organ dysfunction portends a poorer prognosis.

Single-system disease

  • Solitary bone lesions are treated locally with curettage or excision.
  • Painful bone lesions may require intralesional steroid injection (triamcinolone acetonide).
  • Polyostotic bone lesions are best treated with indomethacin or a short course of systemic steroids.27 A case report on pharmacologic management of single-system bony disease using naproxen indicates that multiple COX antagonists may be used in treating this form of Langerhans cell histiocytosis.28
  • Bisphosphonates such as zoledronic acid can also be used to reverse bone destruction and mitigate the pain of bony lesions.29
  • Early treatment with vinblastine and prednisolone has been suggested for bony lesions at vital anatomic locations requiring prompt resolution.11
  • Rarely, lesions that are unusually large and painful occur in inaccessible sites or involve vital structures require radiation therapy (3-6 Gy [300-600 rad]).
  • Localized skin disease is best treated with moderate-to-potent topical steroids (eg, mometasone furoate [Elocon] cream 0.1%, triamcinolone [Kenalog] cream 0.1%, fluocinolone [Synalar] ointment 0.025%) or superpotent topical steroids (eg, clobetasol propionate 0.05%).
  • In cases of severe cutaneous involvement, topical nitrogen mustard (20% solution) may be used.
  • Psoralen plus ultraviolet A (PUVA) is another effective modality for cutaneous-only Langerhans cell histiocytosis or for cutaneous involvement in multisystemic disease. PUVA consists of photosensitizing psoralens (8-methoxypsoralen or 5-methoxypsoralen) either applied topically or ingested systemically 2 h prior to treatment with long-wave ultraviolet A (320-400 nm). The purpose of this treatment is to induce remission of skin diseases by repeated and controlled phototoxic reaction. The photoconjugation of psoralens with DNA produces an antiproliferative reaction in the skin, generates programmed cell death (apoptosis), and induces down-regulation of the cutaneous immune system.30
  • Ultraviolet B excimer laser has been found in at least one case report to offer effective adjuvant therapy in the management of cutaneous Langerhans cell histiocytosis, and it may be particularly useful for patients with comorbidities who cannot tolerate more aggressive treatment.31
  • For single lymph node infiltration, excision is the treatment of choice.
  • Regional lymph node enlargement can be treated with a short course of systemic steroids.
  • Treatment-resistant nodes with sinus tracts to the skin may require systemic chemotherapy.
  • Single-agent chemotherapy with cladribine (2-CDA) may be a promising treatment for single-system pulmonary Langerhans cell histiocytosis.32

Multisystem disease

  • Systemic chemotherapy is indicated for multisystem disease and cases of single-system disease not responsive to other treatment.
  • The combination of cytotoxic drugs and systemic steroids is generally effective. Low-to-moderate doses of methotrexate, prednisone, and vinblastine are used.
  • Thalidomide has also been proposed as an agent for treating refractory/relapsing multisystem disease, but its efficacy appears to be limited to low-risk patients with only skin or bone involvement. Its use also is associated with significant toxicities, including pancytopenia and pulmonary failure.33

Efficacy differences in chemotherapeutic agents

Two large clinical trials have examined differences in efficacy between chemotherapeutic agents.  

  • One cooperative clinical trial in Europe used vinblastine, etoposide, and prednisolone for 6 weeks, followed by mercaptopurine, vinblastine, and prednisolone for 1 year. If soft tissue was involved, treatment was supplemented with etoposide, and, if the patient has organ dysfunction, methotrexate was added. Initial complete resolution occurred in 86% of patients, with a mortality rate of 9% and a disease-free survival rate of 77% at a median follow-up time of 6 years.34
  • The LCH-I trial sponsored by the Histiocyte Society used etoposide or vinblastine for 24 weeks. These agents produced equivalent responses at week 6 and had similar effects on survival and disease recurrence. Lack of response at 6 weeks was associated with an increased likelihood of treatment failure and a worse prognosis. The survival rate was slightly better in the aforementioned European trial than in LCH-I, but the difference was not statistically significant. A greater probability of developing diabetes insipidus occurred in the LCH-I trial.35
  • The LCH-II randomized clinical trial compared the effectiveness of 24 weeks of combined therapy with vinblastine, oral prednisone, and mercaptopurine, versus the same combination with the addition of etoposide. The overall survival in patients treated with etoposide was marginally improved compared with treatment without it; this effect was more pronounced in those patients with risk organ involvement. However, although the addition of etoposide produced slightly more favorable therapeutic responses, it did not decrease the likelihood of disease recurrence.36 Ultimately, the Histiocyte Society concluded that the addition of etoposide to Langerhans cell histiocytosis treatment regimens was of no therapeutic benefit.
  • The LCH-III study is an ongoing, prospective, randomized clinical trial evaluating the efficacy of adding methotrexate to vinblastine and prednisone in the treatment of Langerhans cell histiocytosis in multisystem risk patients. It also includes evaluation of the optimal duration of treatment (6 mo vs 12 mo) using prednisone and vinblastine for multisystem low-risk patients. Finally, it includes a pilot study for patients with single-system multifocal bone disease and localized special sites, including the CNS. Preliminary results of LCH-III have resulted in the following recommendations from the Histiocyte Society, released in February 2008: 
    • Risk patients should be treated with oral prednisone daily and intravenous vinblastine weekly for 6 weeks. Patients who continue to have active disease should repeat this regimen for another 6 weeks. Patients who have no active disease after 6-week induction therapy should begin continuation treatment with oral 6-mercaptopurine daily, supplemented with pulses of oral prednisone and intravenous vinblastine for 12 months of total treatment. The addition of methotrexate to Langerhans cell histiocytosis treatment is not recommended in current practice.
    • Low-risk patients should be treated with oral prednisone and intravenous vinblastine for 12 months total.
    • Patients with multifocal bone disease or CNS risk should be treated with oral prednisone daily and intravenous vinblastine weekly for 6 weeks. Patients should then be supplemented with pulses of oral prednisone and intravenous vinblastine for 6 months of total treatment.
  • The LCH-A-I clinical trial is another open study aimed to define and implement a uniform initial evaluation and stratification of adults with single-system disease, CNS lesions, isolated pulmonary disease, and multisystem Langerhans cell histiocytosis.

Other treatment options

  • In Langerhans cell histiocytosis patients with a very poor prognosis (rapid disease progression, refractory to conventional treatment, or with disseminated risk organ involvement), bone marrow transplantation or reduced-intensity condition stem cell transplantation has shown promise as effective salvage therapy.37,38,39
  • The combination of 2-chlorodeoxyadenosine (2-CDA) and cytosine arabinoside (Ara-C) has also shown promise as an effective combination therapy for refractory multisystem Langerhans cell histiocytosis, but it is associated with considerable bone marrow toxicity.40,41
  • Resistant Langerhans cell histiocytosis may also be treated with a combination of cyclosporin A, antithymocyte globulin, and prednisolone if patients do not have a matched donor for bone marrow transplantation.
  • Other potential treatments include monoclonal antibody targeting with indium In–labeled anti-CD1a, cytokine inhibitors, alemtuzumab, and all-trans retinoic acid.42,43
  • Diabetes insipidus is treated symptomatically with desmopressin acetate (DDAVP).

Consultations

  • Referral to an orthopedic surgeon has important diagnostic and management implications when bone lesions are present.
  • An otolaryngologist may aid in the treatment of otitis media caused by destruction of the temporal and mastoid bones.
  • An ophthalmologist consultation is suggested for a vision check and an assessment of the need of decompression in patients with proptosis.
  • Consultation with a dentist is indicated if loose teeth result from infiltration of the mandibles.
  • Referral to an endocrinologist may help in the design of treatment of the endocrine abnormalities.

Medication

The goals of pharmacotherapy for Langerhans cell histiocytosis (LCH) are to reduce morbidity and to prevent complications.

Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.


Prednisone (Deltasone, Liquid Pred, Meticorten, Orasone, Prednicen-M, Sterapred)

Also known as deltacortisone and deltadehydrocortisone. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Use lowest effective dose in elderly patients. Pediatric dosing depends on condition being treated and response of patient; dose for infants and children should be based on severity and response of the patient rather than on strict adherence to dose indicated by age, weight, or body surface area.

Adult

5-60 mg/d PO qd or divided bid/qid

Pediatric

0.05-2 mg/kg/d PO qd/qid; consider qod for long-term therapy

Ketoconazole, erythromycin, clarithromycin, estrogens, and birth control pills may increase levels
Aminoglutethimide, phenytoin, phenobarbital rifampin, cholestyramine, and ephedrine may decrease levels
Levels of potassium-depleting diuretics (potentiates potassium loss and digitalis toxicity) and cyclosporine may increase; levels of isoniazid, insulin (resistance is induced), and salicylates may decrease; monitor anticoagulant therapy and theophylline levels

Absolute: Systemic fungal infection, herpes simplex keratitis, hypersensitivity (usually with corticotropin, occasionally with IV preparations)
Relative: Hypertension, active TB, CHF, prior psychosis, positive IPPD test result, glaucoma, severe depression, diabetes mellitus, active peptic ulcer disease, cataracts, osteoporosis, recent bowel anastomosis, and pregnancy

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Use lower dose in hypothyroidism, liver disease, and obesity (due to decrease in cortisol-binding globulin increase in free fraction of steroid)
Perform general medical assessment before treatment (a DEXA scan may be useful); check blood pressure; ophthalmologic evaluation may assess and prevent ocular complications; skin tests and/or chest radiographs detect potential for TB reactivation; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use


Prednisolone (AK-Pred, Articulose-50, Delta-Cortef, Econopred, Inflamase)

Also known as delta hydrocortisone, metacortandralone, prednisolone acetate, and prednisolone sodium phosphate. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.

Adult

5-60 mg/d PO/IV/IM

Pediatric

0.1-2 mg/kg/d PO/IV/IM qd or divided bid/qid

Ketoconazole, erythromycin, clarithromycin, estrogens, and birth control pills may increase levels
Aminoglutethimide, phenytoin, phenobarbital, rifampin, cholestyramine, and ephedrine may decrease levels
Levels of potassium-depleting diuretics (potentiates potassium loss and digitalis toxicity) and cyclosporine may increase; levels of isoniazid, insulin (resistance is induced), and salicylates may decrease; monitor anticoagulant therapy and theophylline levels

Absolute: Systemic fungal infection, herpes simplex keratitis, hypersensitivity (usually with corticotropin, occasionally with IV preparations)
Relative: Hypertension, active TB, CHF, prior psychosis, positive IPPD test result, glaucoma, severe depression, diabetes mellitus, active peptic ulcer disease, cataracts, osteoporosis, recent bowel anastomosis, and pregnancy

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use lower dose in hypothyroidism, liver disease, and obesity (due to decrease in cortisol-binding globulin increase in free fraction of steroid)
Perform general medical assessment before treatment (a DEXA scan may be useful); check blood pressure; ophthalmologic evaluation may assess and prevent ocular complications; skin tests and/or chest radiographs detect potential for TB reactivation; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use


Methylprednisolone (Adlone, A-methaPred, depMedalone, Depoject, Depopred)

Also known as 6-alpha-methylprednisolone, methylprednisolone acetate, and methylprednisolone sodium succinate. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation.

Adult

2-60 mg/d PO qd or divided bid/qid initially, followed by gradual dose reduction to lowest possible level consistent with maintaining adequate clinical response
Sodium succinate: 10-80 mg/d IM qd; 10-40 mg IV over several min and repeat IV/IM at intervals depending on clinical response
Sodium acetate: 10-80 mg IM q1-2wk

Pediatric

Sodium succinate: 0.5-1.7 mg/kg/d or 5-25 mg/m2/d PO/IM/IV in divided doses q6-12h
Pulse therapy: 15-30 mg/kg/dose over 30 min or more qd for 3 d

Ketoconazole, erythromycin, clarithromycin, estrogens, and birth control pills may increase levels
Aminoglutethimide, phenytoin, phenobarbital, rifampin, cholestyramine, and ephedrine may decrease levels
Levels of potassium-depleting diuretics (potentiates potassium loss and digitalis toxicity) and cyclosporine may increase; levels of isoniazid, insulin (resistance is induced), and salicylates may decrease; monitor anticoagulant therapy and theophylline levels

Absolute: Systemic fungal infection, herpes simplex keratitis, hypersensitivity (usually with corticotropin, occasionally with IV preparations)
Relative: Hypertension, active TB, CHF, prior psychosis, positive IPPD test result, glaucoma, severe depression, diabetes mellitus, active peptic ulcer disease, cataracts, osteoporosis, recent bowel anastomosis, and pregnancy

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Store intact vials of methylprednisolone sodium succinate at controlled room temperature
Use lower dose in hypothyroidism, liver disease, and obesity (due to decrease in cortisol-binding globulin increase in free fraction of steroid)
Perform general medical assessment before treatment (a DEXA scan may be useful); check blood pressure; ophthalmologic evaluation may assess and prevent ocular complications; skin tests and/or chest radiographs detect potential for TB reactivation; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Nonsteroidal anti-inflammatory drugs

These agents are the most commonly used medications to control mild to moderate pain and to decrease inflammation.


Indomethacin (Indocin)

Rapidly absorbed; metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation; inhibits prostaglandin synthesis.

Adult

75 mg PO bid/tid; not to exceed 200 mg/d

Pediatric

1-2 mg/kg/d PO divided bid/qid; not to exceed 4 mg/kg/d or 150-200 mg/d

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; may decrease effects of beta-blockers, hydralazine, and captopril; may decrease diuretic effects of furosemide and thiazides; coadministration with anticoagulants may prolong PT (monitor and watch for signs of bleeding); may increase risk of methotrexate toxicity, which can manifest as stomatitis, bone marrow suppression, or nephrotoxicity; coadministration may increase phenytoin levels; probenecid may increase toxicity of NSAIDs

Documented hypersensitivity; GI bleeding; renal insufficiency; thrombocytopenia

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Category D in third trimester of pregnancy; caution in cardiac dysfunction, hypertension, renal or hepatic impairment, epilepsy, history of GI bleeding, patients receiving anticoagulants, and for treatment of JRA in children; 60% of elderly patients develop peptic ulceration and/or hemorrhage

Antineoplastic agents

These agents inhibit cell growth and proliferation.


Mechlorethamine (Mustargen)

Forms interstrand and intrastrand cross-links in DNA, which, in turn, results in miscoding, breakage, and failure of replication, inhibiting cell growth. Dispensed as either an aqueous solution or an ointment. Contents of a 10-mg vial are rehydrated with 50 mL of tap water. Patient should wear protective plastic gloves while applying solution. Unused preparation may be stored in refrigerator.

Adult

Apply to lesion with gauze qd

Pediatric

Not established

Documented hypersensitivity; preexisting profound myelosuppression or infection

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Perform skin test prior to treatment with topical preparation to detect sensitivity (use fresh mechlorethamine 0.1 mg/mL and apply over a 3 X 5-cm area of healthy skin); delayed hypersensitivity reaction may complicate treatment; topical desensitization or application of 10 mg nitrogen mustard in Aquaphor can be used in this circumstance; drug can act in the same manner as UV radiation in inducing low-grade nonmelanoma skin cancers; risk of squamous cell carcinomas and basal cell carcinomas increase 8.6- and 1.8-fold, respectively


Vinblastine (Alkaban-AQ, Velban)

Inhibits microtubule formation, which, in turn, disrupts formation of mitotic spindle, causing cell proliferation to arrest at metaphase.

Adult

4-20 mg/m2 (0.1-05 mg/kg) IV q7-10d or 5 d continuous infusion of 1.4-1.8 mg/m2/d or 0.1-0.5 mg/kg/wk

Pediatric

Administer as in adults

Phenytoin plasma levels may be reduced when administered concomitantly with vinblastine; with mitomycin, toxicity may significantly increase

Documented hypersensitivity; bone marrow suppression

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in patients with impaired liver function and neurotoxicity; when patient is receiving mitomycin C, monitor closely for shortness of breath and bronchospasm; store intact vials under refrigeration (2-8°C) and protect from light


Etoposide (Toposar, VePesid)

Inhibits topoisomerase II and causes DNA strand breakage, causing cell proliferation to arrest in late S or early G2 portion of the cell cycle.

Adult

150-200 mg/m2/d IV qd for 3 d q3wk

Pediatric

60-120 mg/m2/d IV for 3-5 d q3-6wk

May prolong the effects of warfarin and increase the clearance of methotrexate; cyclosporine and etoposide have additive effects in cytotoxicity of tumor cells

Documented hypersensitivity; IT administration may cause death

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

FDA currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered; severe myelosuppression with resulting infection or bleeding may occur; adjust dose in hepatic or renal impairment; store intact vials of injection at room temperature and protect from light; store oral capsules under refrigeration


Mercaptopurine (Purinethol)

Purine analog that inhibits DNA and RNA synthesis, causing cell proliferation to arrest.

Adult

Induction: 2.5-5 mg/kg/d (100-200 mg) PO
Maintenance: 1.5-2.5 mg/kg/d PO; 80-100 mg/m2 PO qd

Pediatric

Maintenance: 75 mg/m2 PO qd

Inhibits anticoagulation effects of warfarin by unknown mechanism; toxicity increases when administered with allopurinol; hepatic toxicity increases when used in combination with doxorubicin

Documented hypersensitivity; severe liver disease; severe bone marrow suppression

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

FDA recommends that procedures for proper handling and disposal of antineoplastic agents be considered; may cause birth defects; caution in patients with prior myelosuppression; patients may be at risk for pancreatitis


Methotrexate (Folex, Rheumatrex)

Antimetabolite that inhibits DNA synthesis and cell reproduction in malignant cells. Adjust dose gradually to attain satisfactory response. Refer to individual protocols; may be administered through various routes.

Adult

30-40 mg/m2/wk to 100-7500 mg/m2 PO/IV/IM, intra-arterially or intrathecally, with leucovorin rescue

Pediatric

5-15 mg/m2/wk PO/IM as single dose or 3 divided doses given 12 h apart

Salicylates, NSAIDS, dipyridamole, probenecid, retinoids, ethanol, triamterene, pyrimethamine, sulfonamides, tetracycline, chloramphenicol, penicillin or other broad-spectrum antibiotics, trimethoprim, dapsone, theophylline, phenytoin, phenothiazines, barbiturates, and nitrofurantoin (impair folic acid absorption), ascorbic acid, phenylbutazone, cyclosporin, aminoglycosides

Pregnancy or desire to get pregnant, active peptic ulcer, alcoholism, primary/secondary immunodeficiency, blood dyscrasias, active hepatitis, cirrhosis, chronic renal failure, active infections
Relative contraindications include history of excessive ethanol intake or substance abuse, increased LFT results, recent hepatitis, diabetes mellitus, obesity, history of heritable liver disease, unreliable patient, CrCl <50 mL/min, males contemplating conception (must discontinue for 3 mo)

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Avoid pregnancy during therapy and for at least 3 mo after cessation of therapy; stop excessive alcohol intake; the need to monitor therapy with repeated liver biopsies is controversial; monitor CBC counts and liver enzyme levels during therapy; discontinue if blood cell counts significantly decrease; aspirin, NSAIDs, or low-dose steroids may be concomitantly administered with methotrexate (possibility of increased toxicity with NSAIDs, including salicylates, has not been tested); caution in obesity
Administer 5- to 10-mg test dose, check CBC count and LFT results in 1 wk; if results are good, continue qwk 1-time 7.5-mg doses (may split if GI upset, ie, 8 am, 8 pm, 8 am dosing); increase dose by 2.5 mg/wk each month; may taper by 2.5 mg/wk each month when decreasing dose to lowest possibility


Cladribine (Leustatin)

Synthetic antineoplastic agent for continuous IV infusion. The enzyme deoxycytidine kinase phosphorylates this compound into active 5+-triphosphate derivative, which, in turn, breaks DNA strands and inhibits DNA synthesis. Disrupts cell metabolism, causing death to resting and dividing cells.

Adult

9 mg/m2/d IV for 5 d at 4-wk intervals suggested

Pediatric

0.3 mg/kg/d for 5 d at 4-wk intervals if patient weight <10 kg

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in patients with history of hematologic or immunologic dysfunction; neurotoxicity may occur; allopurinol can be used prophylactically to prevent hyperuricemia, secondary to tumor lysis; mucositis is documented adverse effect


Cytarabine (Cytosar-U, Tarabine PFS)

Converted intracellularly to active compound cytarabine-5'-triphosphate, which inhibits DNA polymerase. Cell cycle S-phase specific. Blocks progression from G1 to S phase and, in turn, kills cells that undergo DNA synthesis in S phase of cell proliferation cycle.

Adult

1000 mg/m2/d IV for 5 d at 4-wk intervals.

Pediatric

1000 mg/m2/d IV for 5 d at 4-wk intervals.

Decreases effects of gentamicin and flucytosine; other alkylating agents and radiation increase cytarabine toxicity

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

If significant increase in bone marrow suppression, reduce number treatment days; patients with hepatic or renal insufficiencies are at higher risk for CNS toxicity after a high-dose of cytarabine (reduce dose)

Phototherapy agents

PUVA has been a successful therapy for some patients. The goal of treatment is to induce remission of skin diseases by repeated and controlled phototoxic reaction. Photoconjugation of psoralens with DNA produces an antiproliferative reaction in the skin, generates programmed cell death (apoptosis), and induces down-regulation of the cutaneous immune system.


Methoxsalen (8-MOP, Oxsoralen, Oxsoralen Ultra)

Inhibits mitosis by binding covalently to pyrimidine bases in DNA when photoactivated by UV-A. Doses are based on lean body weight.

Adult

Oxsoralen, crystalline: 0.6 mg/kg PO 1.5-2 h before exposure to UV light, at least 48 h apart
Oxsoralen Ultra, liquid: 0.3-0.4 mg/kg PO 1.5-2 h before exposure to UV light, at least 48 h apart

Pediatric

Not established

Toxicity increases with phenothiazines, griseofulvin, nalidixic acid, tetracyclines, thiazides, and sulfanilamide

Documented hypersensitivity; squamous cell cancer; cataract; light sensitive diseases (eg, lupus, porphyria); ingestion of photosensitizing drugs; hepatitic disease; arsenic therapy

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Nausea may follow oral treatment (10% more common with liquid than with crystalline preparations probably because of higher psoralen serum levels); nausea rarely seen in patients taking 5-MOP; overdose phenomena (ie, increased delayed erythema sometimes progressing to burns and blisters) are more common after topical psoralen treatment because of epidermal psoralen concentration; exact application of criteria for dosimetry can minimize these symptoms; adverse effects include acnelike eruptions, subungual hemorrhages, and occasional hypertrichosis of face (are transient changes and disappear with discontinuation of treatment); cutaneous carcinogenesis is major concern from prolonged and repeated PUVA treatment; although early data indicate an increased risk for basal and squamous cell carcinomas, findings indicate such risk for squamous cell carcinoma only; in patients on long-term PUVA, life-time monitoring needs to be considered
Stern et al reported 11 melanomas in 9 patients from the cohort of 1380 patients receiving PUVA treatment (16-center study); data demonstrate that risk for melanoma increases with number of treatments and with time, reaching a relative risk of 5.4 after approximately 15 y from initiation of PUVA

Bisphosphonate derivatives

These agents inhibit bone resorption by osteoclasts and in turn mitigate associated bone pain.


Zoledronate (Zometa)

Used to treat multiple myeloma and solid tumor bone metastases. Also used for hypercalcemia of malignancy. Inhibits bone resorption, possibly by acting on osteoclasts or osteoclast precursors. Median duration of complete response (maintaining normalized calcium levels) and time to relapse reported as 32 and 30 d, respectively. Administer daily calcium and vitamin D when used for multiple myeloma or metastatic bone disease.

Adult

4 mg IV infused over at least 15 min; hydrate patient prior to infusion; repeat dose q3-4wk
CrCl >60 mL/min: 4 mg
CrCl 50-60 mL/min: 3.5 mg
CrCl 40-49 mL/min: 3.3 mg
CrCl 30-39 mL/min: 3 mg

Pediatric

Not established

Concurrent administration with loop diuretics may increase risk of hypocalcemia

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal insufficiency (hold dose with increased CrCl); risk of renal deterioration increased with <15 min IV infusion; flulike syndrome (fever, arthralgias, myalgias, skeletal pain), gastrointestinal reactions, anemia, insomnia, dyspnea, electrolyte and mineral disturbances (eg, low serum phosphate, calcium, magnesium, and potassium levels) may occur

More on Langerhans Cell Histiocytosis

Overview: Langerhans Cell Histiocytosis
Differential Diagnoses & Workup: Langerhans Cell Histiocytosis
Treatment & Medication: Langerhans Cell Histiocytosis
Follow-up: Langerhans Cell Histiocytosis
Multimedia: Langerhans Cell Histiocytosis
References
[ CLOSE WINDOW ]

References

  1. Komp DM. Historical perspectives of Langerhans cell histiocytosis. Hematol Oncol Clin North Am. Mar 1987;1(1):9-21. [Medline].

  2. Egeler RM, Favara BE, van Meurs M, Laman JD, Claassen E. Differential In situ cytokine profiles of Langerhans-like cells and T cells in Langerhans cell histiocytosis: abundant expression of cytokines relevant to disease and treatment. Blood. Dec 15 1999;94(12):4195-201. [Medline].

  3. da Costa CE, Szuhai K, van Eijk R, et al. No genomic aberrations in Langerhans cell histiocytosis as assessed by diverse molecular technologies. Genes Chromosomes Cancer. Mar 2009;48(3):239-49. [Medline].

  4. Willman CL. Detection of clonal histiocytes in Langerhans cell histiocytosis: biology and clinical significance. Br J Cancer Suppl. Sep 1994;23:S29-33. [Medline].

  5. Willman CL, Busque L, Griffith BB, et al. Langerhans'-cell histiocytosis (histiocytosis X)--a clonal proliferative disease. N Engl J Med. Jul 21 1994;331(3):154-60. [Medline].

  6. Coury F, Annels N, Rivollier A, et al. Langerhans cell histiocytosis reveals a new IL-17A-dependent pathway of dendritic cell fusion. Nat Med. Jan 2008;14(1):81-7. [Medline].

  7. Allen CE, McClain KL. Interleukin-17A is not expressed by CD207(+) cells in Langerhans cell histiocytosis lesions. Nat Med. May 2009;15(5):483-4; author reply 484-5. [Medline].

  8. Bank MI, Gudbrand C, Rengtved P, et al. Immunohistochemical detection of the apoptosis-related proteins FADD, FLICE, and FLIP in Langerhans cell histiocytosis. J Pediatr Hematol Oncol. Jun 2005;27(6):301-6. [Medline].

  9. Dina A, Zahava V, Iness M. The role of vascular endothelial growth factor in Langerhans cell histiocytosis. J Pediatr Hematol Oncol. Feb 2005;27(2):62-6. [Medline].

  10. Marchal J, Kambouchner M, Tazi A, Valeyre D, Soler P. Expression of apoptosis-regulatory proteins in lesions of pulmonary Langerhans cell histiocytosis. Histopathology. Jul 2004;45(1):20-8. [Medline].

  11. Windebank KP, Nanduri V. Langerhans Cell Histiocytosis. Arch Dis Child. May 19 2009;[Medline].

  12. Shaffer MP, Walling HW, Stone MS. Langerhans cell histiocytosis presenting as blueberry muffin baby. J Am Acad Dermatol. Aug 2005;53(2 Suppl 1):S143-6. [Medline].

  13. Cunningham MJ, Curtin HD, Jaffe R, Stool SE. Otologic manifestations of Langerhans' cell histiocytosis. Arch Otolaryngol Head Neck Surg. Jul 1989;115(7):807-13. [Medline].

  14. Callebaut W, Demedts M, Verleden G. Pulmonary Langerhans' cell granulomatosis (histiocytosis X): clinical analysis of 8 cases. Acta Clin Belg. Oct 1998;53(5):337-43. [Medline].

  15. Okten A, Mocan H, Erduran E, Aslan Y, Gumele HR, Ozoran Y. Langerhans cell histiocytosis associated with recurrent pneumothorax: a case report. Turk J Pediatr. Jan-Mar 1996;38(1):125-30. [Medline].

  16. Andersson By U, Tani E, Andersson U, Henter JI. Tumor necrosis factor, interleukin 11, and leukemia inhibitory factor produced by Langerhans cells in Langerhans cell histiocytosis. J Pediatr Hematol Oncol. Nov 2004;26(11):706-11. [Medline].

  17. Kawakubo Y, Kishimoto H, Sato Y, et al. Human cytomegalovirus infection in foci of Langerhans cell histiocytosis. Virchows Arch. Feb 1999;434(2):109-15. [Medline].

  18. Kannourakis G, Abbas A. The role of cytokines in the pathogenesis of Langerhans cell histiocytosis. Br J Cancer Suppl. Sep 1994;23:S37-40. [Medline].

  19. Billings TL, Barr R, Dyson S. Langerhans cell histiocytosis mimicking malignant melanoma: a diagnostic pitfall. Am J Dermatopathol. Oct 2008;30(5):497-9. [Medline].

  20. Calming U, Henter JI. Elevated erythrocyte sedimentation rate and thrombocytosis as possible indicators of active disease in Langerhans' cell histiocytosis. Acta Paediatr. Oct 1998;87(10):1085-7. [Medline].

  21. Steiner M, Prayer D, Asenbaum S, et al. Modern imaging methods for the assessment of Langerhans' cell histiocytosis-associated neurodegenerative syndrome: case report. J Child Neurol. Mar 2005;20(3):253-7. [Medline].

  22. Phillips M, Allen C, Gerson P, McClain K. Comparison of FDG-PET scans to conventional radiography and bone scans in management of Langerhans cell histiocytosis. Pediatr Blood Cancer. Jan 2009;52(1):97-101. [Medline].

  23. Satter EK, High WA. Langerhans cell histiocytosis: a review of the current recommendations of the Histiocyte Society. Pediatr Dermatol. May-Jun 2008;25(3):291-5. [Medline].

  24. Favara BE, Feller AC, Pauli M, et al. Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. Med Pediatr Oncol. Sep 1997;29(3):157-66. [Medline].

  25. Weitzman S, Egeler RM. Langerhans cell histiocytosis: update for the pediatrician. Curr Opin Pediatr. Feb 2008;20(1):23-9. [Medline].

  26. Valladeau J, Ravel O, Dezutter-Dambuyant C, et al. Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity. Jan 2000;12(1):71-81. [Medline].

  27. Munn SE, Olliver L, Broadbent V, Pritchard J. Use of indomethacin in Langerhans cell histiocytosis. Med Pediatr Oncol. Apr 1999;32(4):247-9. [Medline].

  28. Goldberg SA, O'Connor SC, Sprinz PG. Prostaglandin inhibitors in the treatment of single-system Langerhans cell histiocytosis: pharmacologic rationale and report of two cases. J Pediatr Hematol Oncol. Oct 2008;30(10):778-80. [Medline].

  29. Montella L, Merola C, Merola G, Petillo L, Palmieri G. Zoledronic acid in treatment of bone lesions by Langerhans cell histiocytosis. J Bone Miner Metab. 2009;27(1):110-3. [Medline].

  30. Sakai H, Ibe M, Takahashi H, et al. Satisfactory remission achieved by PUVA therapy in Langerhans cell hisiocytosis in an elderly patient. J Dermatol. Jan 1996;23(1):42-6. [Medline].

  31. Vogel CA, Aughenbaugh W, Sharata H. Excimer laser as adjuvant therapy for adult cutaneous Langerhans cell histiocytosis. Arch Dermatol. Oct 2008;144(10):1287-90. [Medline].

  32. Lazor R, Etienne-Mastroianni B, Khouatra C, Tazi A, Cottin V, Cordier JF. Progressive diffuse pulmonary Langerhans cell histiocytosis improved by cladribine chemotherapy. Thorax. Mar 2009;64(3):274-5. [Medline].

  33. McClain KL, Kozinetz CA. A phase II trial using thalidomide for Langerhans cell histiocytosis. Pediatr Blood Cancer. Jan 2007;48(1):44-9. [Medline].

  34. Gadner H, Heitger A, Grois N, Gatterer-Menz I, Ladisch S. Treatment strategy for disseminated Langerhans cell histiocytosis. DAL HX-83 Study Group. Med Pediatr Oncol. 1994;23(2):72-80. [Medline].

  35. Gadner H, Grois N, Arico M, et al. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. May 2001;138(5):728-34. [Medline].

  36. Gadner H, Grois N, Potschger U, et al. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. Mar 1 2008;111(5):2556-62. [Medline].

  37. Conter V, Reciputo A, Arrigo C, Bozzato N, Sala A, Aricò M. Bone marrow transplantation for refractory Langerhans' cell histiocytosis. Haematologica. Sep-Oct 1996;81(5):468-71. [Medline].

  38. Steiner M, Matthes-Martin S, Attarbaschi A, et al. Improved outcome of treatment-resistant high-risk Langerhans cell histiocytosis after allogeneic stem cell transplantation with reduced-intensity conditioning. Bone Marrow Transplant. Aug 2005;36(3):215-25. [Medline].

  39. Kesik V, Citak C, Kismet E, Koseoglu V, Akyuz C. Hematopoietic stem cell transplantation in Langerhans cell histiocytosis: case report and review of the literature. Pediatr Transplant. May 2009;13(3):371-4. [Medline].

  40. Bernard F, Thomas C, Bertrand Y, et al. Multi-centre pilot study of 2-chlorodeoxyadenosine and cytosine arabinoside combined chemotherapy in refractory Langerhans cell histiocytosis with haematological dysfunction. Eur J Cancer. Nov 2005;41(17):2682-9. [Medline].

  41. Stine KC, Saylors RL, Saccente S, McClain KL, Becton DL. Efficacy of continuous infusion 2-CDA (cladribine) in pediatric patients with Langerhans cell histiocytosis. Pediatr Blood Cancer. Jul 2004;43(1):81-4. [Medline].

  42. Jordan MB, McClain KL, Yan X, Hicks J, Jaffe R. Anti-CD52 antibody, alemtuzumab, binds to Langerhans cells in Langerhans cell histiocytosis. Pediatr Blood Cancer. Mar 2005;44(3):251-4. [Medline].

  43. Idbaih A, Donadieu J, Barthez MA, et al. Retinoic acid therapy in "degenerative-like" neuro-langerhans cell histiocytosis: a prospective pilot study. Pediatr Blood Cancer. Jul 2004;43(1):55-8. [Medline].

  44. Haupt R, Nanduri V, Calevo MG, et al. Permanent consequences in Langerhans cell histiocytosis patients: a pilot study from the Histiocyte Society-Late Effects Study Group. Pediatr Blood Cancer. May 2004;42(5):438-44. [Medline].

  45. Vrijmoet-Wiersma CM, Kooloos VM, Koopman HM, et al. Health-related quality of life, cognitive functioning and behaviour problems in children with Langerhans cell histiocytosis. Pediatr Blood Cancer. Jan 2009;52(1):116-22. [Medline].

  46. Dunger DB, Broadbent V, Yeoman E, et al. The frequency and natural history of diabetes insipidus in children with Langerhans-cell histiocytosis. N Engl J Med. Oct 26 1989;321(17):1157-62. [Medline].

  47. Grois N, Potschger U, Prosch H, et al. Risk factors for diabetes insipidus in langerhans cell histiocytosis. Pediatr Blood Cancer. Feb 2006;46(2):228-33. [Medline].

  48. Abla O, Weitzman S, Minkov M, et al. Diabetes insipidus in Langerhans cell histiocytosis: When is treatment indicated?. Pediatr Blood Cancer. May 2009;52(5):555-6. [Medline].

  49. Lahey E. Histiocytosis x--an analysis of prognostic factors. J Pediatr. Aug 1975;87(2):184-9. [Medline].

  50. Minkov M, Prosch H, Steiner M, et al. Langerhans cell histiocytosis in neonates. Pediatr Blood Cancer. Nov 2005;45(6):802-7. [Medline].

  51. Aoki M, Aoki R, Akimoto M, Hara K. Primary cutaneous Langerhans cell histiocytosis in an adult. Am J Dermatopathol. Jun 1998;20(3):281-4. [Medline].

  52. Bollini G, Jouve JL, Gentet JC, Jacquemier M, Bouyala JM. Bone lesions in histiocytosis X. J Pediatr Orthop. Jul-Aug 1991;11(4):469-77. [Medline].

  53. Broadbent V, Gadner H, Komp DM, Ladisch S. Histiocytosis syndromes in children: II. Approach to the clinical and laboratory evaluation of children with Langerhans cell histiocytosis. Clinical Writing Group of the Histiocyte Society. Med Pediatr Oncol. 1989;17(6):492-5. [Medline].

  54. Chu T, D'Angio GJ, Favara BE, Ladisch S, Nesbit M, Pritchard J. Histiocytosis syndromes in children. Lancet. Jul 4 1987;2(8549):41-2. [Medline].

  55. de Graaf JH, Egeler RM. New insights into the pathogenesis of Langerhans cell histiocytosis. Curr Opin Pediatr. Feb 1997;9(1):46-50. [Medline].

  56. DiNardo LJ, Wetmore RF. Head and neck manifestations of histiocytosis-X in children. Laryngoscope. Jul 1989;99(7 Pt 1):721-4. [Medline].

  57. Egeler RM, Neglia JP, Puccetti DM, Brennan CA, Nesbit ME. Association of Langerhans cell histiocytosis with malignant neoplasms. Cancer. Feb 1 1993;71(3):865-73. [Medline].

  58. French Langerhans' Cell Histiocytosis Study Group. A multicentre retrospective survey of Langerhans' cell histiocytosis: 348 cases observed between 1983 and 1993. The French Langerhans' Cell Histiocytosis Study Group. Arch Dis Child. Jul 1996;75(1):17-24. [Medline].

  59. Giona F, Caruso R, Testi AM, et al. Langerhans' cell histiocytosis in adults: a clinical and therapeutic analysis of 11 patients from a single institution. Cancer. Nov 1 1997;80(9):1786-91. [Medline].

  60. Gotz G, Fichter J. Langerhans'-cell histiocytosis in 58 adults. Eur J Med Res. Nov 29 2004;9(11):510-4. [Medline].

  61. Helmbold P, Hegemann B, Holzhausen HJ, Klapperstück T, Marsch WC. Low-dose oral etoposide monotherapy in adult Langerhans cell histiocytosis. Arch Dermatol. Oct 1998;134(10):1275-8. [Medline].

  62. Hidayat AA, Mafee MF, Laver NV, Noujaim S. Langerhans' cell histiocytosis and juvenile xanthogranuloma of the orbit. Clinicopathologic, CT, and MR imaging features. Radiol Clin North Am. Nov 1998;36(6):1229-40, xii. [Medline].

  63. Howarth DM, Gilchrist GS, Mullan BP, Wiseman GA, Edmonson JH, Schomberg PJ. Langerhans cell histiocytosis: diagnosis, natural history, management, and outcome. Cancer. May 15 1999;85(10):2278-90. [Medline].

  64. Keen CE. Combined skin lesions. Am J Dermatopathol. Oct 1996;18(5):527-32. [Medline].

  65. Kwon OS, Cho KH, Song KY. Primary cutaneous Langerhans cell histiocytosis treated with photochemotherapy. J Dermatol. Jan 1997;24(1):54-6. [Medline].

  66. Ladisch S. Langerhans cell histiocytosis. Curr Opin Hematol. Jan 1998;5(1):54-8. [Medline].

  67. Lin KD, Lin JD, Hsu HH, Juang JH, Huang MJ, Huang HS. Endocrinological aspects of Langerhans cell histiocytosis complicated with diabetes insipidus. J Endocrinol Invest. Jul-Aug 1998;21(7):428-33. [Medline].

  68. Lindley R, Hoile R, Schofield J, Ashton-Key M. Langerhans cell histiocytosis associated with papillary carcinoma of the thyroid. Histopathology. Feb 1998;32(2):180. [Medline].

  69. Maghnie M, Bossi G, Klersy C, Cosi G, Genovese E, Arico M. Dynamic endocrine testing and magnetic resonance imaging in the long-term follow-up of childhood langerhans cell histiocytosis. J Clin Endocrinol Metab. Sep 1998;83(9):3089-94. [Medline].

  70. McKenna DB, Mooney EE, Young MM, Sweeney EC. Multiple cutaneous reticulohistiocytosis. Br J Dermatol. Sep 1998;139(3):544-6. [Medline].

  71. Ringdén O, Lönnqvist B, Holst M. 12-year follow-up of allogeneic bone-marrow transplant for Langerhans' cell histiocytosis. Lancet. Feb 15 1997;349(9050):476. [Medline].

  72. Risdall RJ, Dehner LP, Duray P, Kobrinsky N, Robison L, Nesbit ME Jr. Histiocytosis X (Langerhans' cell histiocytosis). Prognostic role of histopathology. Arch Pathol Lab Med. Feb 1983;107(2):59-63. [Medline].

  73. Rodriguez-Pereira C, Borras-Moreno JM, Pesudo-Martinez JV, Vera-Roman JM. Cerebral solitary Langerhans cell histiocytosis: report of two cases and review of the literature. Br J Neurosurg. Apr 2005;19(2):192-7. [Medline].

  74. Saunders JG, Eveson JW, Addy M, Bell CN. Langerhans cell histiocytosis presenting as bilateral eosinophilic granulomata in the molar region of the mandible. A case report. J Clin Periodontol. Apr 1998;25(4):340-2. [Medline].

  75. Schultz C, Klouche M, Friedrichsdorf S, Richter N, Kroehnert B, Bucsky P. Langerhans cell histiocytosis in children: does soluble interleukin-2-receptor correlate with both disease extent and activity?. Med Pediatr Oncol. Aug 1998;31(2):61-5. [Medline].

  76. Shian WJ, Shu SG, Chu HY, Chi CS. Langerhans cell histiocytosis: a 10-year review. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. Sep-Oct 1994;35(5):385-90. [Medline].

  77. Stefanato CM, Andersen WK, Calonje E, et al. Langerhans cell histiocytosis in the elderly: a report of three cases. J Am Acad Dermatol. Aug 1998;39(2 Pt 2):375-8. [Medline].

  78. Stern RS, Nichols KT, Väkevä LH. Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). The PUVA Follow-Up Study. N Engl J Med. Apr 10 1997;336(15):1041-5. [Medline].

  79. Willman CL, McClain KL. An update on clonality, cytokines, and viral etiology in Langerhans cell histiocytosis. Hematol Oncol Clin North Am. Apr 1998;12(2):407-16. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

Langerhans cell histiocytosis, LCH, histiocytosis X, Langerhans cell granulomatosis, type II histiocytosis, nonlipid reticuloendotheliosis, Langerhans cells, LCs

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Christopher R Shea, MD, Professor and Chief, Section of Dermatology, Department of Medicine, University of Chicago
Christopher R Shea, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society of Dermatopathology, Arthur Purdy Stout Society, Association of Professors of Dermatology, Chicago Dermatological Society, Dermatology Foundation, Illinois Dermatological Society, International Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Markus D Boos, PhD, Medical Scientist Training Program, Pritzker School of Medicine, University of Chicago
Disclosure: Nothing to disclose.

Medical Editor

Bernice R Krafchik, MBChB, FRCPC, Professor Emeritus, Department of Pediatrics, Section of Dermatology, University of Toronto
Bernice R Krafchik, MBChB, FRCPC is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, Canadian Medical Association, College of Physicians and Surgeons of Ontario, Royal College of Physicians and Surgeons of Canada, and Society for Pediatric Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey Meffert, MD, Assistant Clinical Professor of Dermatology, University of Texas Health Science Center-San Antonio
Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, and Texas Dermatological Society
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.