eMedicine Specialties > Dermatology > Allergy & Immunology
Schnitzler Syndrome: Differential Diagnoses & Workup
Updated: Jun 30, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
Lupus Erythematosus, Acute
Urticarial Vasculitis
Other Problems to Be Considered
Adult-onset Still disease is associated with fever, rash, arthralgias, and/or myalgias. The rash in Still disease is evanescent. The urticarial lesions in Schnitzler syndrome are chronically recurrent. In addition, monoclonal gammopathy does not occur in Still disease.
Systemic lupus erythematosus (SLE) may be associated with urticaria, fever, arthralgia, and an elevated ESR. However, leukopenia, neutropenia, and thrombocytopenia are seen in SLE, compared with the leukocytosis and thrombocytosis in Schnitzler syndrome. Antinuclear antibodies are present in SLE, but not in Schnitzler syndrome. Monoclonal paraprotein would not be expected in SLE.
Urticarial vasculitis can have features of nonpruritic urticaria, persisting for more than 24 hours; myalgia; arthralgia; fever; an elevated ESR; and an increased white blood cell count. Skin biopsy of urticarial vasculitis shows fibrinoid necrosis of vessels and a perivascular neutrophilic infiltrate. Fibrinoid necrosis is rarely seen with Schnitzler syndrome.
Chronic idiopathic urticaria often responds symptomatically to antihistamines and lacks the accompanying systemic features and paraprotein seen in Schnitzler syndrome.
Cryoglobulinemia shows clinical signs and symptoms at cold temperatures and demonstrates the presence of cryoglobulins.
The cryoprin-associated periodic syndromes (CAPS), which include familial cold urticaria, Muckle-Wells syndrome, and chronic infantile neurologic cutaneous articular (CINCA) syndrome, all can have associated fever and rash. Patients with these disorders have onset before adulthood, lack a paraprotein, and have a family history of the disease. Muckle-Wells syndrome is often associated with amyloidosis and deafness. CINCA syndrome may be associated with chronic sterile meningitis and neurological deficits.8
Hyperimmunoglobulin D syndrome shows elevated polyclonal immunoglobulin D levels with onset of recurrent fever, usually in the first year of life.
Delayed pressure urticaria can occasionally be nonpruritic. However, it is not associated with an elevated ESR or an increased white blood cell count, although in severe cases, fever, myalgia, and arthralgias may occur. In addition, anemia is not seen with delayed pressure urticaria.
Waldenström macroglobulinemia shows a lymphoid proliferation in the bone marrow, and the monoclonal IgM gammopathy is found in large amounts, usually more than 10,000 mg/L. Often, it is associated with hepatosplenomegaly. In Schnitzler syndrome, the monoclonal gammopathy is less than that seen in Waldenström macroglobulinemia.
Workup
Laboratory Studies
- All cases are associated with an IgM monoclonal gammopathy, which is demonstrated by serum immunoelectrophoresis. Most cases are of the IgM-kappa isotype. A few cases of IgM-lambda and IgM-kappa/lambda have occurred. The serum IgM levels are usually less than 10 g/L. In 51% of cases, serum protein electrophoresis may not detect the IgM gammopathy because the levels can be very low. A small number of cases have been presented in the literature wherein the patient had clinical features of Schnitzler syndrome but had an associated IgG gammopathy rather than an IgM gammopathy—an IgG variant of Schnitzler syndrome.9,10
- The ESR and C-reactive protein level are elevated in most cases. Leukocytosis (70%), thrombocytosis (20%), and anemia (50%) may also be found.
- Abnormal lymphoid proliferation can be seen in 20% of bone marrow biopsy samples, with nonspecific polyclonal lymphocytic and plasmacytic infiltrates.
Imaging Studies
- Radiologic evaluation shows evidence of hyperostosis in 35% of Schnitzler syndrome patients. Often, the areas of hyperostosis coincide with areas of symptomatic bone pain, such as the iliac bone, tibia, femur, and vertebral columns.
Histologic Findings
A review of the pathology of Schnitzler syndrome shows that the histopathologic findings are not consistent; features in some patients include a superficial dermal and perivascular infiltrate of polymorphonuclear cells, mostly neutrophils, suggestive of neutrophilic urticaria. A small percentage of specimens demonstrate a superficial perivascular mononuclear infiltrate suggestive of chronic urticaria and lymphocytic inflammation. Vessels are intact, and dilatation of dermal lymphatics with mild superficial edema may present.
Rare cases show fibrin deposition, extravasation of erythrocytes, or leukocytoclastic vasculitis.
Deposits of IgM and complement in the upper dermis and/or at the dermoepidermal junction are seen in 45% of cases. Rarely are IgM deposits found within vessel walls.
More on Schnitzler Syndrome |
| Overview: Schnitzler Syndrome |
 Differential Diagnoses & Workup: Schnitzler Syndrome |
| Treatment & Medication: Schnitzler Syndrome |
| Follow-up: Schnitzler Syndrome |
| References |
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References
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de Koning HD, Bodar EJ, van der Meer JW, Simon A,. Schnitzler syndrome: beyond the case reports: review and follow-up of 94 patients with an emphasis on prognosis and treatment. Semin Arthritis Rheum. Dec 2007;37(3):137-48. [Medline].
Asli B, Bievenu B, Cardoliani F, et al. Chronic Urticaria and Monoclonal IgM gammopathy (Schnitzler Syndrome). Report of 11 cases treated with Pefloxacin. Arch Dermatol. 2007;143:1046-1050.
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Olsen E, Forre O, Lea T, Langeland T. Unique antigenic determinants (idiotypes) used as markers in a patient with macroglobulinemia and urticaria. Similar idiotypes demonstrated in the skin and on peripheral blood lymphocytes. Acta Med Scand. 1980;207(5):379-84. [Medline].
Saurat JH, Schifferli J, Steiger G, Dayer JM, Didierjean L. Anti-interleukin-1 alpha autoantibodies in humans: characterization, isotype distribution, and receptor-binding inhibition--higher frequency in Schnitzler's syndrome (urticaria and macroglobulinemia). J Allergy Clin Immunol. Aug 1991;88(2):244-56. [Medline].
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Simon A, van der Meer JWM, Drenth JPH. Familial auto-inflammatory syndromes. In: Harris ED, Budd RC, Firestein GS. Kelley's textbook of Rheumatology. 7th. Philadelphia: Saunders; 2004:Chapter 112 pp1773-88.
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de Koning HD, Bodar EJ, Simon A, van der Hilst JC, Netea MG, van der Meer JW. Beneficial response to anakinra and thalidomide in Schnitzler's syndrome. Ann Rheum Dis. Apr 2006;65(4):542-4. [Medline].
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Ramadan KM, Eswedi HA, El-Agnaf MR. Schnitzler syndrome: A case report of successful treatment using the anti-CD20 momoclonal antibody rituximab. Br J Dermatol. 2007;156:1072-74.
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Martinez-Taboada VM, Fontalba A, Blanco R, Fernandez-Luna JL. Successful treatment of refractory Schnitzler syndrome with anakinra: comment on the article by Hawkins et al. Arthritis Rheum. Jul 2005;52(7):2226-7. [Medline].
Bonnetblanc JM, Drouet M, Laplaud P, Bedane C, Bernard P. Urticaria with macroglobulinaemia. Disease activity associated alterations in immunoglobulins profile and bone marrow hypodiploidy. Dermatologica. 1990;181(1):41-3. [Medline].
Borradori L, Rybojad M, Puissant A, Dallot A, Verola O, Morel P. Urticarial vasculitis associated with a monoclonal IgM gammopathy: Schnitzler's syndrome. Br J Dermatol. Jul 1990;123(1):113-8. [Medline].
Harati A, Brockmeyer NH, Altmeyer P, Kreuter A. Skin disorders in association with monoclonal gammopathies. Eur J Med Res. Mar 29 2005;10(3):93-104. [Medline].
Machet L, Vaillant L, Machet MC, Reisenleiter M, Goupille P, Lorette G. Schnitzler's syndrome (urticaria and macroglobulinemia): evolution to Waldenström's disease is not uncommon. Acta Derm Venereol. Sep 1996;76(5):413. [Medline].
Nashan D, Sunderkotter C, Bonsmann G, Luger T, Goerdt S. Chronic urticaria, arthralgia, raised erythrocyte sedimentation rate and IgG paraproteinaemia: a variant of Schnitzler's syndrome?. Br J Dermatol. Jul 1995;133(1):132-4. [Medline].
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Further Reading
Keywords
Schnitzler syndrome, Schnitzler's syndrome, chronic urticaria, nonpruritic urticaria, monoclonal immunoglobulin M gammopathy, monoclonal IgM gammopathy
