Undifferentiated Connective-Tissue Disease Medication

  • Author: Bernard Hildebrand, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Jan 19, 2012
 

Medication Summary

Nonsteroidal anti-inflammatory drugs (NSAIDs), antimalarials (eg, hydroxychloroquine), and corticosteroids are the mainstay of therapy in patients with undifferentiated connective-tissue disease (UCTD). Immunosuppressive drugs are generally reserved for treating specific clinical manifestations and when there is major organ involvement.

Mosca et al (2008) found that 93% of patients with UCTD were initially treated with corticosteroids and/or antimalarials, and 2% were started on immunosuppressive medications. After 10 years of follow-up, 16% of patients were no longer receiving therapy, 36% were being treated with hydroxychloroquine plus corticosteroids, 10% were taking corticosteroids alone, and no patients were receiving cytotoxic immunosuppressive therapy.[18]

Bodolay et al (2003) prescribed low-dose corticosteroids only when NSAIDs were deemed ineffective.[15] Common indications for systemic corticosteroids included recurrent serositis, skin vasculitis, and synovitis. Antimalarials were administered for photosensitivity and severe rash. The authors concluded that aggressive immunosuppressive therapy for "true" UCTD is neither necessary nor justified.

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Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Class Summary

NSAIDs may be beneficial for analgesic, antipyretic, anti-inflammatory, or antiplatelet effects. These medications inhibit the enzyme cyclooxygenase, resulting in a generalized decrease in prostaglandin production, ultimately reducing pain and inflammation. Other mechanisms may also exist, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.

Arthritis and arthralgias may respond to NSAIDs alone or in combination with an antimalarial (see below).

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Naproxen (Naprosyn)

 

For relief of mild-to-moderate pain. Inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.

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Nonsteroidal Anti-Inflammatory Drug (NSAID), Cox-2 Selective

Class Summary

The inducible cyclooxygenase-2 (COX-2) isoenzyme is produced during inflammatory conditions, resulting in increased production of proinflammatory prostaglandins that cause pain and swelling. COX-2 inhibitors selectively block the COX-2 isoenzyme and may minimize adverse effects associated with traditional NSAIDs (eg, gastrointestinal bleeding).

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Celecoxib (Celebrex)

 

Selectively inhibits cyclooxygenase-2 and reduces prostaglandin synthesis

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Antimalarials

Class Summary

These agents may inhibit the chemotactic properties of pro-inflammatory leukocytes (eg, polymorphonuclear cells, lymphocytes). They may also interfere with intracellular processing of autoantigenic peptides.

Antimalarials may be used with or without NSAIDs to control arthralgias/arthritis, constitutional symptoms, and mucocutaneous manifestations.

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Hydroxychloroquine (Plaquenil)

 

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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Corticosteroids

Class Summary

Corticosteroids inhibit the cascade of inflammatory and immune mechanisms at the cellular level, resulting in profound anti-inflammation and modification of the immune response. The pharmacologic effects and adverse effects of corticosteroids are influenced by the drug preparation, dose, dosing schedule, and route of administration. They vary with the individual patient and disease process.

These drugs are commonly used in combination with other medications to control the signs and symptoms of inflammation.

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Prednisone (Deltasone, Orasone, Meticorten)

 

Immunosuppressant for treatment of autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

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Immunosuppressant agents

Class Summary

These agents suppress key factors of the immune system and are typically reserved for severe manifestations of UCTD.

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Methotrexate (Rheumatrex, Folex PFS)

 

Unknown mechanism of action. Analog of folic acid and inhibits dihydrofolate reductase and, ultimately, DNA synthesis. Methotrexate also inhibits the enzyme 5-aminoimidazole-4-carboxamidoribonucleotide (AICAR) transformylase, leading to intracellular accumulation of AICAR and extracellular adenosine release. The adenosine has anti-inflammatory properties.

Methotrexate is very effective in the treatment of inflammatory arthritis and other systemic manifestations of UCTD. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness).

Available as 2.5-mg tab or 25-mg/mL vial.

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Azathioprine (Imuran)

 

A purine analog that interferes with the synthesis of adenosine and guanine resulting in inhibited synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells and may be effective for treatment of articular and extra-articular manifestations of connective-tissue disease.

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Calcium channel blockers

Class Summary

These agents relax vascular smooth muscle and decrease peripheral vascular resistance. They may help control the signs and symptoms of Raynaud phenomenon.

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Nifedipine (Procardia, Procardia XL, Adalat CC)

 

During depolarization, inhibits calcium ions from entering the slow channels and voltage-sensitive areas of vascular smooth muscle.

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Diltiazem (Cardizem, Cardizem SR)

 

During depolarization, inhibits calcium ions from entering the slow channels and voltage-sensitive areas of vascular smooth muscle.

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Contributor Information and Disclosures
Author

Bernard Hildebrand, MD  Chief of Rheumatology, Mike O'Callaghan Federal Hospital, Nellis Air Force Base

Bernard Hildebrand, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, and American Society for Bioethics and Humanities

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel F Battafarano, DO, FACP, FACR  Clinical Professor of Medicine, University of Texas Health Science Center at San Antonio; Associate Professor of Medicine, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Chief of Rheumatology Service, San Antonio Military Medical Center

Daniel F Battafarano, DO, FACP, FACR is a member of the following medical societies: American College of Physicians, American College of Rheumatology, and Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Elliot Goldberg, MD  Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology

Disclosure: Nothing to disclose.

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

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Table 1. Preliminary Classification Criteria for Undifferentiated Connective-Tissue Disease
Inclusion CriteriaClinical



Exclusion Criteriaa



Laboratory Exclusion Criteriaa
1. Signs and symptoms suggestive of a CTD but not fulfilling the diagnostic or classification criteria for any of the defined CTDs b for at least 3 years c



2. Presence of antinuclear antibodies determined on two different occasions



Malar rash



Subacute cutaneous lupus



Discoid lupus



Cutaneous sclerosis



Heliotrope rash



Gottron papules



Erosive arthritis



Anti-dsDNA



Anti-Smith



Anti-U1-RNP



Anti-Scl70



Anticentromere



Anti-La/SSB



Anti-Jo1



Anti-Mi2



Table 2. Predictors of Progression to Definite Connective-Tissue Disease
Connective-Tissue Disease AssociationSigns or SymptomsLaboratory Data
Systemic lupus erythematosusAge, fever, photosensitivity, serositis, alopeciaANA, Anti-dsDNA, Anti-Smith, Anti-cardiolipin antibodies, Coombs positivity, leukopenia
Systemic sclerosisSclerodactyly, Raynaud phenomenon, sicca symptoms, esophageal dysfunctionANA with nucleolar pattern
Sjögren syndromeXerostomia, xerophthalmia, Raynaud phenomenonAnti-SSA, Anti-SSB
Rheumatoid arthritisSymmetric polyarthritisRF, elevated ESR (>70 mm/h)
Mixed connective-tissue diseaseEsophageal reflux, polyarthritis, Raynaud phenomenonANA, Anti-U1-RNP
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