eMedicine Specialties > Rheumatology > Miscellaneous Inflammatory Arthritis

Mediterranean Fever, Familial: Differential Diagnoses & Workup

Author: John O Meyerhoff, MD, Assistant Professor, Department of Internal Medicine, Johns Hopkins University School of Medicine; Clinical Scholar in Rheumatology, Department of Medicine, Sinai Hospital of Baltimore
Contributor Information and Disclosures

Updated: Nov 13, 2009

Differential Diagnoses

Acute Rheumatic Fever
Nephrolithiasis
Appendicitis
Pericarditis, Acute
Calcium Pyrophosphate Deposition Disease
Pleurodynia
Gout
Systemic Lupus Erythematosus
Lyme Disease

Other Problems to Be Considered

Familial Hibernian fever
Hyperimmunoglobulin D and periodic fever syndrome

Workup

Laboratory Studies

  • Results of routine blood tests performed during the acute attacks of familial Mediterranean fever (FMF) are nonspecific. Levels of acute-phase reactants (ie, C-reactive protein, amyloid A protein, fibrinogen) are elevated, as is the erythrocyte sedimentation rate. The WBC count is usually elevated during an attack. The elevated levels rapidly return to the reference range as the attack abates.
  • Proteinuria should raise a concern about possible amyloidosis. For unknown reasons, hematuria occurs in 5% of patients.
  • Synovial fluid is inflammatory, with cell counts as high as 100,000/µL.
  • Genetic testing is now available for FMF.
    • Testing for a limited number of genes may be appropriate in patients with a known ethnic background. Complete gene sequencing may be more helpful in patients of mixed or unknown ethnicity.
    • Symptomatic patients with at least one MEFV mutation should be considered to have FMF.
    • Patients with no gene mutations who meet criteria for FMF should be offered a trial of colchicine.
    • Given the high gene frequency and low penetrance in certain populations (eg, Ashkenazi Jews, Armenians), gene testing should be closely correlated to clinical findings to avoid false-positive results.

Imaging Studies

  • Findings during an acute attack in patients with peritonitis, pleuritis, and arthritis are as expected and include air-fluid levels, pleural effusions, and synovial effusions.

Procedures

  • Amyloidosis can be presumed in patients with FMF, particularly those of North African descent who have proteinuria. Renal biopsy or, alternatively, submucosal rectal biopsy, is indicated in these patients.

Histologic Findings

Massive amyloid infiltration of the blood vessels and of the endothelial side of the glomerular basement membrane occurs in the kidneys. In the rectal submucosa, the amyloid is found near the blood vessels.

More on Mediterranean Fever, Familial

Overview: Mediterranean Fever, Familial
Differential Diagnoses & Workup: Mediterranean Fever, Familial
Treatment & Medication: Mediterranean Fever, Familial
Follow-up: Mediterranean Fever, Familial
References
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References

  1. Gershoni-Baruch R, Brik R, Shinawi M, Livneh A. The differential contribution of MEFV mutant alleles to the clinical profile of familial Mediterranean fever. Eur J Hum Genet. Feb 2002;10(2):145-9. [Medline]. [Full Text].

  2. Tomiyama N, Higashiuesato Y, Oda T, et al. MEFV mutation analysis of familial Mediterranean fever in Japan. Clin Exp Rheumatol. Jan-Feb 2008;26(1):13-7. [Medline].

  3. Kim S, Ikusaka M, Mikasa G, et al. Clinical study of 7 cases of familial Mediterranean fever with MEFV gene mutation. Intern Med. 2007;46(5):221-5. [Medline]. [Full Text].

  4. Lidar M, Livneh A. Familial Mediterranean fever: clinical, molecular and management advancements. Neth J Med. Oct 2007;65(9):318-24. [Medline]. [Full Text].

  5. Lidar M, Kedem R, Langevitz P, et al. Intravenous colchicine for treatment of patients with familial Mediterranean fever unresponsive to oral colchicine. J Rheumatol. Dec 2003;30(12):2620-3. [Medline].

  6. Mor A, Pillinger MH, Kishimoto M, et al. Familial Mediterranean fever successfully treated with etanercept. J Clin Rheumatol. Feb 2007;13(1):38-40. [Medline].

  7. Roldan R, Ruiz AM, Miranda MD, et al. Anakinra: new therapeutic approach in children with Familial Mediterranean Fever resistant to colchicine. Joint Bone Spine. Jul 2008;75(4):504-5. [Medline].

  8. Tunca M, Akar S, Soyturk M, et al. The effect of interferon alpha administration on acute attacks of familial Mediterranean fever: A double-blind, placebo-controlled trial. Clin Exp Rheumatol. Jul-Aug 2004;22(4 Suppl 34):S37-40. [Medline].

  9. Tweezer-Zaks N, Rabinovich E, Lidar M, et al. Interferon-alpha as a treatment modality for colchicine- resistant familial Mediterranean fever. J Rheumatol. Jul 2008;35(7):1362-5. [Medline].

  10. Calguneri M, Apras S, Ozbalkan Z, et al. The efficacy of continuous interferon alpha administration as an adjunctive agent to colchicine-resistant familial Mediterranean fever patients. Clin Exp Rheumatol. Jul-Aug 2004;22(4 Suppl 34):S41-4. [Medline].

  11. Ben-Chetrit E, Berkun Y, Ben-Chetrit E, et al. The outcome of pregnancy in the wives of men with familial mediterranean fever treated with colchicine. Semin Arthritis Rheum. Oct 2004;34(2):549-52. [Medline].

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  13. Lidar M, Kedem R, Mor A, et al. Arthritis as the sole episodic manifestation of familial Mediterranean fever. J Rheumatol. May 2005;32(5):859-62. [Medline].

  14. Livneh A, Langevitz P, Zemer D, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum. Oct 1997;40(10):1879-85. [Medline].

  15. Livneh A, Langevitz P, Zemer D, et al. The changing face of familial Mediterranean fever. Semin Arthritis Rheum. Dec 1996;26:612-27. [Medline].

  16. Majeed HA, El-Khateeb M, El-Shanti H, et al. The spectrum of familial Mediterranean fever gene mutations in Arabs: report of a large series. Semin Arthritis Rheum. Jun 2005;34(6):813-8. [Medline].

  17. Meyerhoff J. Familial Mediterranean fever: report of a large family, review of the literature, and discussion of the frequency of amyloidosis. Medicine (Baltimore). Jan 1980;59(1):66-77. [Medline].

  18. Samuels J, Aksentijevich I, Torosyan Y, et al. Familial Mediterranean fever at the millennium. Clinical spectrum, ancient mutations, and a survey of 100 American referrals to the National Institutes of Health. Medicine (Baltimore). Jul 1998;77:268-97. [Medline].

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Further Reading

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Keywords

familial Mediterranean fever, FMF, recurrent polyserositis, periodic fever syndrome, amyloidosis, secondary amyloidosis, colchicine therapy, colchicine, appendicitis, peritonitis, amyloid nephropathy, MEFV gene, pyrin, marenostrin, amyloid A, serum amyloid A, nephrotic syndrome, paroxysm, renal vein thrombosis, proteinuria, vasculitis, arthritis, myalgia syndrome, peritonitis, pleuritis, peritoneum, seronegative spondyloarthropathy, chemotactic factor

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Contributor Information and Disclosures

Author

John O Meyerhoff, MD, Assistant Professor, Department of Internal Medicine, Johns Hopkins University School of Medicine; Clinical Scholar in Rheumatology, Department of Medicine, Sinai Hospital of Baltimore
John O Meyerhoff, MD is a member of the following medical societies: American College of Physicians and American College of Rheumatology
Disclosure: Pfizer  Honoraria Speaking and teaching

Medical Editor

Carlos J Lozada, MD, Director of Rheumatology Fellowship Program, Associate Professor, Department of Medicine, Division of Rheumatology and Immunology, Jackson Memorial Medical Center, University of Miami School of Medicine
Carlos J Lozada, MD is a member of the following medical societies: American College of Physicians and American College of Rheumatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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.

CME Editor

Alex J Mechaber, MD, FACP, 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, Professor of Medicine, Temple University 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: medifocus Honoraria Review panel membership; health dialogs Honoraria Consulting; West Penn Allegheny Health System None Board membership

 
 
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