Schnitzler Syndrome—A Rare Enigma
Abstract & Commentary
Synopsis: Schnitzler syndrome is an idiopathic illness characterized by chronic urticaria, intermittent fever, bone pain, arthralgia or arthritis, and a monoclonal IgM gammopathy.
Source: Lipsker D, et al. The Schnitzler syndrome. Four
new cases and review of the literature. Medicine (Baltimore). 2001;80:37-44.
Let us say you were faced with a 50-year-old man or woman with a chronic urticaria rash, appearing as rose pale macules associated with a fever up to 104°, morning stiffness, arthralgia of the hands, and occasional night sweats. Sometimes the rash resolved within 12 hours. Findings were confined to the rash and axillary and inguinal lymph nodes.
Laboratory findings could include a moderate or marked leukocytosis, elevation of the sedimentation rate and C-reactive protein, monoclonal IgM gammopathy with an absent Bence Jones proteinuria, increased interleukin-6, but normal tumor necrosis factor (TNF). Complement studies and a search for auto-antibodies are negative. Skin biopsy showed a neutrophilic infiltration but no immunoglobulin infiltration.
The patient, let us say, is unresponsive to antihistamines, colchicines, aspirin, prednisone, chlorambucil, aketoprofen, cetirizine, and hydroxyzine. The rash continued for years and the IgM increased gradually over the years.
Comment by Joseph f. john, md
Specialists who don’t recognize this syndrome should not feel bad. Schnitzler syndrome was not described until 1972 and since then, including the 4 new cases described by Lipsker and colleagues from Strasbourg, there has been a total of 52 cases described in the literature. The unrelenting continual skin rash combined with an IgM gammopathy is the hallmark of the syndrome and is usually accompanied by a constellation of symptoms or signs. The diagnostic criteria include urticarial skin rash plus monoclonal IgM spike and 2 of the following: fever; arthralgia; bone pain; palpable lymph nodes; liver or spleen enlargement; increased ESR; leukocytosis; and abnormal bone morphology.
The rash is distinctive with pale rose-colored papules. The trunk and limbs are most often involved. The fever, though intermittent, may peak higher than 104° and disable patients. The fever may respond, to a degree, to nonsteroidal medications.
It is not known if the clonal IgM elevation is primary in nature or a response to some antigentic stimulation. The current report used modern insights to discover an elevation of IL-6 and/or IL-2 receptor levels.
The musculoskeletal complaints may be centered around either joint or bone pain. Amyloidosis, as Lipsker et al point out, does not occur, but patients may develop a lymphoproliferative disorder such as a lymphoma, IgM myeloma, or even Waldenström’s disease.
Treatment remains very disappointing, and after reviewing the gamut of therapeutic trials, Lipsker et al concluded that no therapy is predictably useful. The intensity of the skin rash may respond to PUVA therapy. Bone and joint pain may respond to NSAIDs.
It is not surprising that readers may not recognize this syndrome: the mean time in delay of diagnosis was 5 years! The major differential diagnoses include tuberculosis, lupus, lymphoma, adult onset Still’s disease, cryoglobulinemia, acquired C1 inhibitor deficiency, hyper IgD syndrome, chronic infantile neurologic cutaneous and articular syndrome, and Muckle-Wells syndrome.
Regarding etiology, I would be surprised if the ultimate cause of this syndrome is not microbial. Indeed, in the cases described by Lipsker et al, there has been inadequate study of these patients for presence of DNA viruses or of retroviruses. The few number of cases preclude clinical trials.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content