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Chronic Urticaria and Monoclonal Igm Gammopathy (Schnitzler Syndrome) Report of 11 Cases Treated with Pefloxacin

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Chronic Urticaria and Monoclonal Igm Gammopathy (Schnitzler Syndrome) Report of 11 Cases Treated with Pefloxacin OBSERVATION Chronic Urticaria and Monoclonal IgM Gammopathy (Schnitzler Syndrome) Report of 11 Cases Treated With Pefloxacin Bouchra Asli, MD; Boris Bienvenu, MD; Florence Cordoliani, MD; Jean-Claude Brouet, MD, PhD; Yurdagul Uzunhan, MD; Bertrand Arnulf, MD; Marion Malphettes, MD; Michel Rybojad, MD; Jean-Paul Fermand, MD Background: Schnitzler syndrome is characterized by duced in 6 patients. In 9 patients, pefloxacin was chronic urticarial rash and monoclonal IgM gammopathy administered for more than 6 months (Յ10 years), with and is sometimes associated with periodic fever, arthral- a good safety profile. gias, and bone pain. Current treatment is unsatisfactory. Conclusions: Pefloxacin therapy can be considered for Observations: Eleven patients with Schnitzler syn- patients with Schnitzler syndrome because it usually im- drome were treated with oral pefloxacin mesylate (800 proves chronic urticaria and the systemic symptoms of mg/d). In 10 patients, we observed a dramatic and sus- the disease. tained improvement of urticarial and systemic manifes- tations. Corticosteroid therapy could be stopped or re- Arch Dermatol. 2007;143(8):1046-1050 HE FEATURES OF SCHNITZ- METHODS ler syndrome include chronic nonpruriginous After the first patient, the drug was proposed to urticaria and monoclonal all patients who were referred to us and ful- IgM gammopathy. Inter- filled the following criteria: (1) recurrent urti- mittentT fever, asthenia, arthralgia, and bone carial rash persisting more than 2 months; pain with imaging evidence of osteoscle- (2) presence of a serum monoclonal IgM; (3) a rosis also occur frequently. Biological find- serum complement level within the reference ings usually include an increase in white range and no detectable cryoglobulinemia; blood cell count and erythrocyte sedimen- (4) no associated systemic disease; and (5) no contraindication to treatment with quinolone tation rate, which reflect an inflamma- agents. All patients gave informed consent. tory syndrome and the presence of the Between January 1, 1995, and December 31, monoclonal IgM. 2005, 11 patients (including the index case) Skin biopsy findings often include were enrolled in the study. Before initiation of mononuclear or neutrophilic perivascu- treatment and while receiving pefloxacin, pa- lar infiltrates. The link between urticaria, tients were asked to note daily any symptom, systemic symptoms, hyperostosis, and the particularly skin changes, and their tempera- monoclonal B-cell proliferation is un- ture. They also had to note changes in dos- ages of any drug being used. Pefloxacin me- known. Current treatment is unsatisfac- sylate was administered orally at an initial tory. The use of systemic corticosteroids dosage of 800 mg/d. may be effective but is hampered by cor- ticodependence, with well-known atten- dant adverse effects. Chemotherapy may RESULTS induce myelodysplasia. Many other thera- Author Affiliations: Service pies have been proposed in the context of PATIENTS d’Immunohe´matologie isolated case reports. (Drs Asli, Brouet, Arnulf, We observed a dramatic and sus- The main characteristics of the 11 pa- Malphettes, and Fermand) and tained improvement of manifestations of tients are summarized in Table 1. Age at Service de Dermatologie Schnitzler syndrome in a patient who was (Drs Cordoliani and Rybojad), diagnosis of Schnitzler syndrome ranged Hoˆpital Saint Louis, and Service treated with pefloxacin mesylate for a uri- from 44 to 80 years (mean age, 57.5 years). de Me´decine Interne, Hoˆpital nary tract infection. This prompted our All patients presented with chronic urti- Cochin (Dr Bienvenu), study of the efficacy of the antibiotic in 10 caria, with a disease duration of 4 months Paris, France. other consecutive patients. to 16 years (mean duration, 4.6 years). Re- (REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 8), AUG 2007 WWW.ARCHDERMATOL.COM 1046 ©2007 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 current urticarial wheals usually consisted of sharply de- marcated, raised maculopapular erythematous lesions that Table 1. Main Characteristics of the 11 Patients predominated on the lower limbs and abdomen and were With Urticarial Rash asymptomatic. The wheals lasted from several hours to 1 week and were separated by periods of remission of vari- Characteristic No. of Patients ous durations. Skin biopsy specimens showed few peri- Fever 9 vascular mononuclear or polymorphonuclear cells with Weight loss 5 Fatigue 8 or without mild edema (in 8 patients) and a clear peri- Arthralgia or arthritis 11 vascular infiltrate with leukocytoclastic vasculitis but with- Bone pain 9 out necrosis (in 2 patients). Skin biopsy results were nor- Abnormal findings on bone morphology 8a mal in 1 patient. Serum monoclonal IgM componentb 11 In 9 patients, some urticarial wheals were accompa- ESRϾ30 mm/hc 10 d nied by spiking fever (Յ40°C). In these cases, arthral- CRP levelϾ15 mg/L 11 Ͼ e gias, myalgias (n=11), fatigue (n=7), and weight loss Fibrin level 4 g/L 11 LeukocytosisϾ10 000 cells/µLf 10 (n=5) were typical. Such symptoms, particularly an un- Hemoglobin levelϽ11.0 g/dLg 3 usual fatigue, were also reported by 1 of the nonfebrile Platelet countϾ400ϫ103/µLh 7 patients. Nine patients reported bone pain, usually in the Serum albumin levelϽ3.5 g/dLi 4 lower back, pelvis, and lower limbs, with radiographic evidence of bone densification and hyperfixation appar- Abbreviations: CRP, C-reactive protein; ESR, erythrocyte sedimentation rate. ent on technetium Tc 99m scan findings in 2 of 7 and 8 SI conversion factor: To convert CRP to nanomoles per liter, multiply by of 9 patients, respectively. Increase in the erythrocyte sedi- 9.524. mentation rate, hyperfibrinemia, decreased albumin- a Among the 9 patients who underwent bone survey. emia, polymorphonuclear hyperleukocytosis, hypochro- b Includes IgM ␬ light chains in 10 and ␭ light chains in 1. c Median ESR, 83 mm/h; range, 30 to 134 mm/h. mic anemia, and thrombocytosis were frequent (Table 1). d Median CPR level, 92 mg/L; range, 25 to 215 mg/L. Results of searches for an infectious process or a con- e Median fibrin level, 7.1 g/L; range, 4.3 to 8.0 g/L. nective tissue disorder were consistently negative. In all f Median leukocyte count, 11 900 cells/µL; range, 10 300 to 28 100 cells/µL. cases, test results for cryoglobulin and antinuclear anti- g Median hemoglobin level, 10.1 g/dL. bodies were negative, and the serum level of the C3 h Median platelet count, 488ϫ103/µL; range, 439ϫ103/µL to complement component was within the reference range. 608ϫ103/µL. i Serum C4 level was within the reference range in all but Median albumin level, 3.2 g/dL; range, 2.5 to 3.5 g/dL. 1 patient, in whom a heterozygous deficiency was docu- mented. In all studied cases, results of searches for an- tibodies against hepatitis B or C viruses were negative. steroids were active against urticaria and systemic symp- A monoclonal serum IgM was detected in all pa- toms in all 7 treated patients when a precise threshold tients. At diagnosis, the IgM level was low (Յ0.5 g/dL), dosage was used; this threshold dosage varied from one intermediate (Ͼ0.5 to Ͻ2 g/dL), and high (Ն2 g/dL) in patient to the next. The required mean daily dose of pred- 4, 6, and 1 patient, respectively. During follow-up, the nisone equivalent was 11.5 mg/d (range, 5-30 mg/d). De- serum IgM level was higher than 2 g/dL in the 3 patients spite this treatment, persisting flares usually occurred, who developed an overt Waldenstro¨m macroglobulin- requiring a transient increase of the corticosteroid dose. emia (WM). The monoclonal IgM bore ␬ light chains in Chlorambucil or cyclophosphamide was given to 4 pa- 10 patients and ␭ light chains in 1. Results of bone mar- tients without a corticosteroid-sparing effect or any im- row aspirate and/or biopsy, available in 10 of the 11 pa- provement, including in the 3 patients with overt MW. tients, were normal in 7 and disclosed a lymphoplasma- Two of these patients achieved a partial remission, as as- cytic infiltrate typical of WM in 3. At the first examination, sessed by decreases of 60% and 75% in the serum IgM small superficial lymph nodes were noted in the 3 pa- level, whereas the last patient had a resistant disease. In tients with WM, 2 of whom also had splenomegaly. Chest one patient, repeated plasma exchanges were ineffec- radiogram, ultrasound examination results, or com- tive. In another, psoralen–UV-A therapy was ineffective puted tomography did not disclose enlarged mediasti- as well. nal or abdominal lymph nodes in any patient. In all cases, oral pefloxacin mesylate therapy, 400 mg twice a day, was begun during an urticarial flare and was TREATMENT added to the patient’s previous treatment. The antibi- otic significantly reduced urticarial wheals, with a con- As reported in Table 2, before enrollment in the study, comitant sensation of improved condition, in all but pa- patients had received a wide class of medications, in- tient 7. The improvement occurred within 24 hours of cluding nonsteroidal anti-inflammatory drugs, antihis- taking the first tablet for 6 patients and within 48 to 72 tamines, colchicine, dapsone, and hydrochloroquine or hours for the others. Fever, when present, disappeared chloroquine hydrochloride. Although questionable and or decreased before the subsequent progressive clearing transient improvement was sometimes observed, these of the urticarial lesions. drugs were globally ineffective, particularly for control- In all but patient 7, pefloxacin mesylate was used as a ling the rash. The only patient who received thalido- maintenance treatment, initially at a dose of 800 mg/d. mide experienced a clear improvement, but the therapy In all cases, it significantly reduced the frequency and in- was stopped because of peripheral neuropathy. Cortico- tensity of the disease manifestations. This was exempli- (REPRINTED) ARCH DERMATOL/ VOL 143 (NO.
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