Multicentric Reticulohistiocytosis Medication

Updated: Dec 29, 2015
  • Author: Alisa N Femia, MD; Chief Editor: Herbert S Diamond, MD  more...
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Medication

Medication Summary

No drug of choice is known for multicentric reticulohistiocytosis (MRH). Most patients are treated with oral prednisone, with or without a cytotoxic/immunosuppressive agent, such as methotrexate, cyclophosphamide, or chlorambucil, or a TNF-alpha antagonist. Most of the previously reported therapies are as listed below.

First-line therapies

These include the following agents:

  • Methotrexate [6, 9, 21, 57]
  • Systemic corticosteroids (eg, prednisone, prednisolone, dexamethasone high-dose pulse)
  • Intralesional corticosteroids (eg, triamcinolone acetonide)
  • NSAIDs (eg, aspirin, indomethacin)

Second-line therapies

  • Psoralen plus ultraviolet light (PUVA)
  • Antimalarials (eg, chloroquine, hydroxychloroquine [21] )
  • Cyclophosphamide [6]
  • Chlorambucil
  • Azathioprine
  • Vincristine
  • Topical nitrogen mustard
  • Leflunomide [22]
  • TNF-alpha antagonists [23] (eg, etanercept, [11] infliximab [17] ): TNF-alpha has been found to be increased in the synovium of patients with MRH, providing a rationale for this therapy [24]
  • Bisphosphonate drugs (eg, alendronate, zoledronic acid [25] )
  • Concomitant combinations of several of the above therapies [21]
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Corticosteroids

Class Summary

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

Prednisone (Rayos)

Prednisone is an immunosuppressant for treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear cell activity. It stabilizes lysosomal membranes and suppresses lymphocytes and antibody production. Although prednisone is regularly used, it has not been proven to be effective.

Prednisolone (Millipred, Orapred, Orapred ODT, Prelone)

Corticosteroids act as potent inhibitors of inflammation. They may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body.

Dexamethasone acetate (Baycadron)

This agent decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reducing capillary permeability. Dosage varies with the degree of inflammation and the size of the affected area.

Triamcinolone (Kenalog-10, Kenalog-40, Aristospan)

Triamcinolone can be used topically or injected intralesionally. It decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability.

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Analgesic Nonsteroidal Anti-inflammatory Drug (NSAIDs)

Class Summary

These agents have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action may be inhibition of cyclo-oxygenase (COX) activity and prostaglandin synthesis. Other mechanisms, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions, may also exist.

Indomethacin (Indocin)

Indomethacin is rapidly absorbed; metabolism occurs in the liver by demethylation, deacetylation, and glucuronide conjugation. This agent inhibits prostaglandin synthesis.

Ibuprofen (I-Prin, Advil, Motrin)

Ibuprofen is the drug of choice for mild to moderately severe pain. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Naproxen (Anaprox, Naprelan, Naprosyn)

Naproxen is used for relief of mild to moderately severe pain. It inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which is responsible for prostaglandin synthesis.

Ketoprofen

Ketoprofen is used for the relief of mild to moderate pain and inflammation. Small doses are indicated initially in patients with small body size, elderly patients, and persons with renal or liver disease. Doses of over 75 mg do not increase therapeutic effects. Administer high doses with caution, and closely observe the patient for response.

Flurbiprofen

Flurbiprofen may inhibit cyclooxygenase, thereby inhibiting prostaglandin biosynthesis. These effects may result in analgesic, antipyretic, and anti-inflammatory activities.

Diclofenac (Voltaren XR, Cataflam, Cambia)

This is one of a series of phenylacetic acids that has demonstrated anti-inflammatory and analgesic properties in pharmacological studies. It is believed to inhibit the enzyme cyclooxygenase, which is essential in the biosynthesis of prostaglandins. Diclofenac can cause hepatotoxicity; hence, liver enzymes should be monitored in the first 8 weeks of treatment. It is absorbed rapidly; metabolism occurs in the liver by demethylation, deacetylation, and glucuronide conjugation. The delayed-release, enteric-coated form is diclofenac sodium, and the immediate-release form is diclofenac potassium.

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Cytotoxic/Immunosuppressive Agents

Class Summary

Cytotoxic/immunosuppressive agents inhibit key factors in the immune system that are responsible for inflammatory responses. None have been documented to be effective in MRH, except in anecdotal reports.

Methotrexate (Rheumatrex, Trexall)

Methotrexate has an unknown mechanism of action in the treatment of inflammatory reactions; it may affect immune function. This agent ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust the dose gradually to attain a satisfactory response.

Cyclophosphamide

Cyclophosphamide is chemically related to nitrogen mustards. As an alkylating agent, its mechanism of action may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells.

Azathioprine (Imuran, Azasan)

Azathioprine is a purine analog that inhibits the synthesis of deoxyribonucleic acid (DNA), RNA, and proteins. It may decrease the proliferation of immune cells, resulting in lower immunologic activity.

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Disease-Modifying Antirheumatic Drugs

Class Summary

Disease-modifying antirheumatic drugs (DMARDs) can retard or prevent disease progression and, thus, joint destruction and subsequent loss of function.

Leflunomide (Arava)

Leflunomide is an immunomodulatory agent. It inhibits pyrimidine synthesis, which, in turn, results in antiproliferative and anti-inflammatory effects.

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Antimalarials

Class Summary

Derivatives of 4-aminoquinoline are active against various autoimmune disorders.

Hydroxychloroquine (Plaquenil)

Although this agent has not been demonstrated to be effective in studies, anecdotal reports suggest a possible effect. Hydroxychloroquine inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions.

Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.

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Antineoplastics, Other

Class Summary

Individual case reports suggest a benefit from the use of TNF-antagonists in MRH.

Vincristine (Vincasar PFS)

The mechanism of action of vincristine is uncertain. It may involve a decrease in reticuloendothelial cell function or an increase in platelet production.

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TNF antagonists

Class Summary

Individual case reports suggest a benefit from the use of TNF-antagonists in MRH.

Adalimumab (Humira)

Adalimumab is a recombinant human immunoglobulin G1 (IgG1) monoclonal antibody specific for human TNF. It is indicated for the reduction of inflammation and the inhibition of structural damage progression in moderate to severe rheumatoid arthritis. This agent is reserved for patients who experience an inadequate response to 1 or more disease-modifying antirheumatic drugs (DMARDs).

Adalimumab can be used alone or in combination with methotrexate or other DMARDs. It binds specifically to TNF-alpha and blocks interaction with p55 and p75 cell-surface TNF receptors.

Infliximab (Remicade)

Infliximab neutralizes the cytokine TNF-alpha and inhibits it from binding to the TNF-alpha receptor. Consult a rheumatologist concerning its use.

Etanercept (Enbrel)

Etanercept is a soluble p75 TNF-receptor fusion protein (sTNFR-Ig). It inhibits TNF binding to cell-surface receptors, thereby decreasing inflammatory and immune responses.

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Bisphosphonates

Class Summary

These agents are analogues of pyrophosphate and act by binding to hydroxyapatite in the bone matrix, thereby inhibiting the dissolution of crystals. Bisphosphonates prevent osteoclast attachment to the bone matrix and osteoclast recruitment and viability.

Alendronate (Fosamax)

Alendronate inhibits bone resorption via actions on osteoclasts or osteoclast precursors. Used to treat osteoporosis in men and women, it may reduce bone resorption and the incidence of fracture in the spine, hip, and wrist by approximately 50%.

Alendronate should be taken with a large glass of water at least 30 minutes before eating and drinking, to maximize absorption. Because of possible esophageal irritation, patients must remain upright after taking the medication. Since it is renally excreted, alendronate is not recommended for use in patients with moderate to severe renal insufficiency, ie, creatinine clearance (CrCl) below 30 mL/min or above 3 mg/dL. Consequently, its use in perirenal transplantation is limited.

Pamidronate (Aredia)

Pamidronate's main action is to inhibit the resorption of bone. The mechanism by which this inhibition occurs is not fully known. The drug is adsorbed onto calcium pyrophosphate crystals and may block the dissolution of these crystals, also known as hydroxyapatite, which are an important mineral component of bone. There is also evidence that pamidronate directly inhibits osteoclasts.

Risedronate (Actonel, Atelvia)

Risedronate is a potent aminobisphosphonate that principally acts by inhibiting osteoclastic bone resorption.

Tiludronate (Skelid)

Tiludronate is a sulfur-containing bisphosphonate of intermediate potency between etidronate and newer nitrogen-containing bisphosphonates.

Zoledronate (Reclast, Zometa)

Zoledronate inhibits bone resorption. It inhibits osteoclastic activity and induces osteoclastic apoptosis

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