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Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by chronic urticarial rash and monoclonal immunoglobulin M (IgM) or IgG gammopathy. Viruses, including COVID-19, activate the innate immune system, therefore SchS, in which the innate immune system is improperly activated, is hypothesized to be exacerbated by viral infection. However, there were no reported SchS cases exacerbated by any viral infection. Here, we report a SchS case with an unusual IgA gammopathy manifested and exacerbated by COVID-19 infection. This report advocates the need for recognizing unusual cases of SchS with monoclonal IgA, and following up on paraprotein like IgA even when it is initially undetectable in cases with SchS symptoms. We also hypothesize that existing autoinflammatory diseases may be exacerbated by COVID-19 infection in the case of a combination of these diseases., (© 2024 Japanese Dermatological Association.)

Neutrophilic urticarial dermatosis (NUD) is a rare form of dermatosis that is poorly understood. It was first described by Kieffer and colleagues as an urticarial eruption that is histopathologically characterized by a perivascular and interstitial neutrophilic infiltrate with intense leukocytoclasia and without vasculitis or dermal edema. NUD clinically presents as a chronic or recurrent eruption that consists of nonpruritic macules, papules, or plaques that are pink to reddish and that resolve within 24 hours without residual pigmentation. NUD is often associated with systemic diseases such as Schnitzler syndrome, lupus erythematosus, adult-onset Still's disease, and cryopyrin-associated periodic syndromes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Schnitzler syndrome (SchS) is a rare, acquired, autoinflammatory disease that is sometimes associated with a fever of unknown origin (FUO). Elevated alkaline phosphatase (ALP) stemming from abnormal bone remodeling is a characteristic laboratory finding of SchS and is included in the diagnostic criteria. However, its utility as a clue to the diagnosis of SchS has been under-emphasized. We herein report a case of SchS presenting with a FUO and highly elevated ALP concentration, which led to repeated, unnecessary liver biopsies.

Schnitzler's Syndrome (SS) is a rare late-onset acquired autoinflammatory disorder which consists of chronic urticaria associated with a monoclonal IgM-kappa gammopathy, arthralgias, skeletal hyperostosis, lymphadenopathy, and recurrent constitutional symptoms. The average age of diagnosis is 51 years with a slight male predominance with a male to female ratio of 1.6. Diagnosis of SS requires the presence of 2 major criteria including chronic urticaria and monoclonal IgM along with at least two of the following minor criteria: recurrent intermittent fevers, bone pain, arthralgias, elevated erythrocyte sedimentation rate (ESR), neutrophilic dermal infiltrate on skin biopsy, and leukocytosis or elevated C-reactive protein (CRP). Early diagnosis and clinical awareness are paramount in SS as it is associated with a 15-20% risk of lymphoproliferative malignancy. The median overall survival is 12.8 years. We present a case of a 39-year-old female with new onset urticaria associated with recurrent fevers and joint pain. Symptoms were refractory to steroids, and high dose antihistamines. Multi-disciplinary evaluation resulted in the ultimate diagnosis of Schnitzler's Syndrome. The patient was ultimately treated with canakinumab (Il-1 inhibitor), with near resolution of symptoms. This case demonstrates the importance of a broad differential diagnosis and maintaining a high clinical suspicion for rare diseases when presented with a complex form of an otherwise common condition., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Schnitzler syndrome is a rare acquired autoinflammatory syndrome. It presents with an urticarial rash and a monoclonal gammopathy, usually of the IgM kappa type. In addition, patients can present with bone and/or joint pain, recurrent fever, asthenia, weight loss, myalgia, headache, lymphadenopathy, hepatomegaly, or splenomegaly. An elevation of blood inflammation markers is commonly found. Skin biopsy of the urticarial rash reveals neutrophilic infiltrate, known as neutrophilic urticarial dermatosis. To confirm the diagnosis, two sets of diagnostic criteria have been established. The syndrome shares many features with other autoinflammatory disorders, such as adult-onset Still's disease and NLRP3-auto-inflammatory disorders (NLRP3-AID, formerly known as cryopyrin-associated periodic syndromes, or CAPS). The pathogenesis of the disease is not yet fully understood; however, it is believed that interleukin (IL)-1β plays a crucial role and explains the excellent effectiveness of IL-1 blocking agents. It is a chronic disease, and some patients develop lymphoproliferative disease, and seldom AA amyloidosis.

Background: Schnitzler's syndrome is a rare, acquired and probably underdiagnosed disorder. It is a type of autoinflammatory condition with late onset., Case Presentation: A man in his fifties had had recurrent urticaria, fever and chronic joint pain during the previous year. After an extensive investigation, no evidence of infection, autoimmune disease or malignancy was found. Blood samples showed moderately elevated SR and CRP, mild thrombocytosis and presence of monoclonal IgM in low concentration (MGUS). The combination of sterile inflammation, joint/muscle pain, urticaria and M-component was consistent with Schnitzler's syndrome. He was placed on a treatment trial with anakinra (interleukin [IL]-1 receptor antagonist) 100 mg x 1 daily, given as a subcutaneous injection. His condition was excellent until one week after the first injection. The initial treatment indicated a good clinical effect of IL-1 blockade, but due to the very unpleasant localised side effects (extensive dermatitis), treatment with anakinra was withdrawn, and canakinumab (monoclonal antibody against IL-1β) was chosen instead. He responded very well to this treatment and experienced no adverse effects. One year after starting treatment, the patient still has an excellent treatment response., Interpretation: Anakinra is the treatment of first choice for this condition, but this case history illustrates that canakinumab can be tried if anakinra is not tolerated by the patient.

Schnitzler syndrome (SS) is a rare autoinflammatory disease that presents with chronic urticaria and monoclonal immunoglobulin (Ig) M or G, accompanied by fever, abnormal bone remodeling, skin biopsy with a neutrophilic dermal infiltrate, leukocytosis, or elevated C-reactive protein. It is usually refractory to antihistamines and immunosuppression. We present a case report of clinical SS without monoclonal Ig with robust response to interleukin-1 inhibitor anakinra. This suggests the possible existence of an incomplete form of SS and underlines the risk of false negative diagnosis in individuals with such "incomplete SS".

Objective: To describe a new autoinflammatory syndrome with recurrent fever and monoclonal gammopathy that differs from Schnitzler syndrome., Methods: We conducted a retrospective study of patients with monoclonal gammopathy and recurrent fever of unknown origin., Results: Five patients were studied; median age at onset of symptoms was 44 years. Median frequency of fever attacks was 6 episodes per year. In the absence of treatment, the median duration of fevers was 3 days., Conclusion: This new autoinflammatory syndrome is defined by an association among monoclonal gammopathy, arthralgias, and recurrent fever.

The Schnitzler syndrome (SS) is a rare and underdiagnosed entity that associates a chronic urticarial rash, monoclonal IgM (or sometimes IgG) gammopathy and signs and symptoms of systemic inflammation. During the past 45 years the SS has evolved from an elusive, little-known disorder to the paradigm of a late-onset auto-inflammatory acquired syndrome. Though there is no definite proof of its precise pathogenesis, it should be considered as an acquired disease involving abnormal stimulation of the innate immune system, which can be reversed by the interleukin 1 (IL-1) receptor antagonist anakinra. Here we describe the case of a 56-year-old male Caucasian patient affected by SS and hospitalized several times in our unit because of relapsing episodes of acute kidney injury. He underwent an ultrasound-guided percutaneous kidney biopsy in September 2012, which showed the histologic picture of type I membranoproliferative glomerulonephritis. He has undergone conventional therapies, including nonsteroidal anti-inflammatory drugs, steroids and immunosuppressive drugs; more recently, the IL-1 receptor antagonist anakinra has been prescribed, with striking clinical improvement. Although the literature regarding kidney involvement in the SS is lacking, it can however be so severe, as in the case reported here, to lead us to recommend the systematic search of nephropathy markers in the SS., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Neutrophilic urticarial dermatosis (NUD) is a rare form of dermatosis. In clinical terms, it consists of a chronic or recurrent eruption comprising slightly elevated, pink to reddish plaques or macules. The elementary lesion lasts 24 to 48hours and resolves without leaving any residual pigmentation. Extra-cutaneous signs are common, particularly fever or arthralgia. At histopathology, the dermis contains dense neutrophilic interstitial infiltrate with leukocytoclasis, but without fibrinoid necrosis of vessel walls. NUD often occurs in a setting of underlying systemic disease. The most commonly associated diseases are adult-onset Still's disease, Schnitzler syndrome, lupus erythematosus and cryopyrin-associated periodic syndromes. Treatment of NUD depends on the clinical context. Dapsone and colchicine are often effective., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Schnitzler syndrome is a very rare acquired systemic disease with many similarities to hereditary autoinflammatory syndromes. The main characteristics are generalized exanthema and a monoclonal gammopathy with IgM. Other clinical features include fever, muscle, bone and/or joint pain, and lymphadenopathy. About 15-20% of patients with Schnitzler syndrome develop lymphoproliferative diseases and, in rare cases, amyloid A (AA) amyloidosis can occur if the disease is not treated. Activation of the innate immune system, especially interleukin(IL)-1β, is central in the pathogenesis of the disease. Consequently, complete control of disease symptoms can be achieved in 80% of patients by treatment with the IL-1 receptor antagonist anakinra.

Patients with HHV-8-negative/idiopathic multicentric Castleman disease (iMCD) experience systemic inflammatory symptoms and polyclonal lymphoproliferation due to an unknown etiology. Schnitzler's syndrome (SS) is characterized by recurrent urticarial rash, monoclonal IgM gammopathy, and other clinical signs of inflammation. To our knowledge, we report the first case of iMCD associated with SS and the fourth case of anakinra inducing a complete response for an iMCD patient. A forty-four year old woman with a history of a recurrent urticarial rash, presented to our hospital complaining of 6 months of night sweats, fever, chronic urticaria, iliac bone pain, and generalized lymphadenopathy. An IgM Kappa monoclonal component was measured at 7.8g/L. A lymph node biopsy revealed histopathological features consistent with the plasma cell variant of iMCD. She was diagnosed with SS and iMCD. Anti-IL-1 treatment with anakinra (100mg/day) was introduced. Within 48h, we observed improvement in the fever and the urticarial rash. By one month, we considered the patient in complete remission. Two years later, the remission is persistent while the patient is still under therapy. Though this is only the fourth reported case of anakinra in iMCD, this is yet another case demonstrating the effectiveness of anti-IL-1 blockade in SS. We hypothesize that uncontrolled cytokine production is responsible for both the SS and the iMCD. The etiologies of SS and iMCD are unknown, and future research is necessary., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Schnitzler syndrome (SS) is an autoinflammatory dermatosis that often goes undiagnosed for 5-6 years. Patients typically carry a diagnosis of urticaria; however, their cutaneous symptoms fail to respond to typical urticaria therapies and lack symptoms such as pruritus. Additionally, patients with SS may see multiple providers for nonspecific complaints of fever, lymphadenopathy, arthralgias, and bone pain. A correct diagnosis is paramount, as close to 20% of patients may develop a lymphoproliferative disorder and appropriate treatment may ameliorate all symptoms.1 We report 2 cases of SS misdiagnosed as urticaria for years in order to illuminate diagnostic pearls, histopathological findings, and treatment modalities. Additionally, we highlight the importance of neurologic disturbances in this rare but important differential diagnosis of urticaria.

J Drugs Dermatol. 2017;16(6):625-627.

Background: Schnitzler syndrome (SS) is a rare autoinflammatory disorder characterized by a recurrent urticarial rash and a monoclonal immunoglobulin M gammopathy, as well as 2 of the following minor criteria: recurrent fever (>38°C), objective signs of abnormal bone remodeling, elevated C-reactive protein level or leukocytosis, and a neutrophilic infiltrate on skin biopsy. Alternatively, a monoclonal immunoglobulin G gammopathy may be present along with 3 minor criteria for diagnosis., Objective: To report a rare case of SS without monoclonal gammopathy and inform physicians of this possible clinical presentation so that treatment is not delayed., Methods: We report a case of a 62-year-old white man with a clinical diagnosis of SS without monoclonal gammopathy. He presented with chronic urticaria unresponsive to conventional therapy., Results and Conclusions: To our knowledge, there have only been 3 case reports of SS in the absence of monoclonal gammopathy documented in the literature. SS should be considered based on clinical presentation, even in the absence of monoclonal gammopathy, to facilitate appropriate management., (© The Author(s) 2016.)

Background: Neutrophilic urticarial dermatosis (NUD) comprises a particular autoinflammatory condition within the spectrum of aseptic neutrophilic dermatoses characterized by a distinct urticarial eruption clinically and a neutrophilic dermatosis histopathologically., Objective: In this study, we reviewed skin biopsies of lesional skin of patients seen in our outpatient clinic for autoimmune dermatoses and in allergy department from 1982 to 2014 that fulfilled these criteria., Methods: A total of 77 biopsies from 50 patients were analyzed histopathologically. Included were cases of Schnitzler syndrome, Still disease, systemic lupus erythematosus, Sjögren syndrome, cryopyrin-associated periodic syndrome, primary biliary cirrhosis, inflammatory bowel disease, and those that had signs of systemic inflammation not otherwise specified, that is, fever, arthritis, leukocytosis, and elevated erythrocyte sedimentation rate. A control cohort was defined as including a total of 70 biopsies from 50 patients comprising neutrophilic urticaria (pressure-induced and not pressure-induced), conventional urticaria, lupus erythematosus expressing neutrophils, and exanthematous drug reaction of macular type expressing neutrophils., Results: Skin biopsies of NUD revealed a perivascular and interstitial neutrophilic infiltrate focally extending into the epithelia of epidermis, hair follicles, sebaceous and sweat glands, a feature which we termed neutrophilic epitheliotropism. This neutrophilic epitheliotropism proved to be of high sensitivity (83.1%) and lower specificity (74.3%). The histological findings could be substantiated by immunohistochemical markers for leukocytes (elastase and myeloperoxidase), in particular in cases where neutrophils showed uncharacteristic band-like nuclei., Conclusions: Neutrophilic epitheliotropism is a new sensitive and specific histopathological clue for NUD, a histopathological reaction pattern within the spectrum of neutrophilic dermatoses that needs to be differentiated from conventional urticaria.

Systemic urticaria are defined as urticaria, most often chronic, associated with systemic diseases. At present time, urticarial vasculitis and neutrophilic urticarial dermatosis associated to autoinflammatory syndromes are not considered to be subtypes of chronic spontaneous urticaria due to their distinctly clinical and histological characteristics as well different pathomechanisms. Sometimes, chronic urticaria is associated to thyroid autoimmunity. However, the majority of cases of chronic spontaneous urticaria have no discernible cause and further investigations are not necessary, as already suggested by some authors and French consensus conference more than 10 years ago., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: Chronic urticaria is a common disorder characterized by recurrent wheals, angioedema, or both. Several differential diagnoses need to be considered in patients presenting with wheals and/or angioedema. These include rare diseases such as autoinflammatory syndromes and urticarial vasculitis in patients with recurrent wheals and bradykinin-mediated angioedema in patients with recurrent swellings. AIM AND RESULT: In order to not miss these conditions, we have developed a symptom-based diagnostic algorithm for the management of patients with wheals and/or angioedema., Discussion and Conclusion: By asking the right questions and performing a limited diagnostic workup as suggested here, this algorithm may help to establish the right diagnosis and treat patients early and more effectively., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Schnitzler syndrome is a rare clinical entity characterized by the association of chronic urticarial rash and monoclonal immunoglobulin M gammopathy. A 62-year old male developed nephrotic syndrome with Schnitzler syndrome. A renal biopsy revealed mild thickening of the glomerular basement membrane with spikes and mild expansion of the mesangial matrix; prominent fine granular immunoglobulin G depositions were found along the capillary walls by immunofluorescence study and electron dense deposits were observed in the subepithelial spaces and in a part of mesangium by electron microscopically. The histological findings were compatible with secondary form of membranous nephropathy. To the best of our knowledge this is the first renal biopsy case of Schnitzler syndrome. With corticosteroid treatment chronic rash and proteinuria have disappeared, but immunoglobulin (IgM) paraprotein has been still present.

Schnitzler syndrome is a rare plasma cell disorder the pathogenesis of which is still not fully understood. We evaluated the circulating levels of four major angiogenic cytokines (VEGF, angiogenin, angiopoietin-1 and angiopoietin-2) and six bone remodeling markers (sRANKL, osteoprotegerin, dickkopf-1, CTX, osteocalcin and bone-specific alkaline phosphatase-bALP) in 13 patients with Schnitzler syndrome. At diagnosis, patients had elevated angiogenic cytokines. The mean VEGF levels were almost 3.5-fold higher in Schnitzler syndrome compared to controls, while 10 of 13 patients had higher VEGF than the upper control value. Successful treatment led to a significant reduction in VEGF. Patients with Schnitzler syndrome had increased bone formation (high bALP, osteocalcin and osteoprotegerin) which was not balanced by an increase in bone resorption (normal CTX and sRANKL). These data support a role for VEGF as a new minor criterion in the diagnosis and follow up of Schnitzler syndrome, while the uncoupling of bone remodeling in favor of bone formation justifies the presence of bone densification.

Hereditary periodic fever syndromes, also called autoinflammatory syndromes, are characterized by relapsing fever and additional manifestations such as skin rashes, mucosal manifestations, or arthralgias. Some of these disorders present without fever but with the associated systemic manifestations. The responsible mutated genes have been identified for most of these disorders, which lead to the induction of the uncontrolled and excessive production of interleukin-1beta (IL-1beta). The inhibition of IL-1beta through IL-1 receptor antagonist or monoclonal antibody against IL-1beta is used with success in most of these diseases. In case of TNF-receptor associated periodic syndrome (TRAPS) and paediatric granulomatous arthritis (PGA), TNF-antagonists may also be used; in familial Mediterranean fever (FMF) colchicine remains the first choice.

Schnitzler Syndrome (SS) is a rare clinical entity of unknown etio-pathogenesis characterizated by non itching chronic urticaria, associated with an IgM monoclonal paraprotein; other symptoms as bone pain, poliarthralgia, elevated erytrocyte sedimentation rate and persistent fever, may be present. Since 1972-1974, when it was first described by Schnitzler et al. about 80 cases have been reported in literature, all characterized by chronic urticaria and IgM monoclonal gammopathy. Nashan et al, were the first to publish a case of SS with a benign monoclonal IgG, composed by light -κ- chains. We described two cases of chronic non itching urticaria with the same symptoms above mentioned, but an IgG monoclonal paraprotein instead of IgM gammopathy. Therefore in according to Nashan et al, we suggest that the spectrum of SS should include patients that present the same clinical picture described in 1972 in association with either IgM or IgG gammopathy.

Schnitzler syndrome is a rare condition defined by chronic urticaria, osteosclerotic bone lesions, and monoclonal IgM gammopathy. Schnitzler syndrome can precede the onset of a true lymphoproliferative disorder including Waldenström macroglobulinemia and rarely systemic marginal zone B-cell lymphoma. We describe a case of intractable chronic urticaria accompanied by a retroperitoneal neoplasm. IgM monoclonal gammopathy, lumber pain, intermittent fever, and elevation of C-reactive protein were the clues for the diagnosis of Schnitzler syndrome. An evaluation for malignancy using systemic computed tomography scan and fluorodeoxyglucose positron emission tomography revealed the retroperitoneal tumor, and a subsequent bone-marrow aspirate confirmed the diagnosis of B-cell lymphoma. Combined rituximab and radiotherapy ameliorated the skin symptoms. This case indicates that a detailed search for malignant neoplasms might be required for the long-term management of Schnitzler syndrome, and that B-cell lymphomas may contribute to the pathogenesis of this condition.

Schnitzler syndrome is a rare disease characterised by chronic urticaria and arthralgia. The recent evidence that the IL-1 receptor antagonist IL-1Ra could induce rapid and complete remission of Schnitzler symptoms has pointed to IL-1 as a major pathological factor in this disease. To examine the possibility that Schnitzler syndrome may be considered to be an autoinflammatory disease, in this study we measured the serum levels of IL-18, another cytokine of the IL-1 family that is cleaved by caspase-1, in two recently diagnosed Schnitzler patients before and after treatment with IL-1Ra. In parallel, mRNA expression of IL-1 family cytokines and caspase-1 were assessed in isolated blood monocytes. Treatment with IL-1Ra significantly inhibited IL-1beta gene expression, indicating that IL-1beta activity in Schnitzler syndrome is central to IL-1beta gene upregulation in a type of auto-amplification loop. While no IL-1beta was detected in serum, free circulating IL-18 was increased in patients with Schnitzler syndrome, despite low IL-18 gene expression in monocytes. This suggests constitutive activation of the IL-1beta/IL-18-producing inflammasome, and supports the hypothesis that Schnitzler's syndrome is a new autoinflammatory disease.

Schnitzler syndrome is characterized by monoclonal IgM gammopathy, urticaria, recurrent fever, evidence of inflammation, bone pain, and arthralgia, occasionally in combination with lymphadenopathy and/or hepatosplenomegaly. Only about 80 cases have been reported to date. Development of a hematological malignancy is the main complication. Recent reports of remissions induced by IL-1 receptor antagonist therapy shed new light on the pathophysiology of the disease.

A 44-year-old man presented with a 2-year history of an intermittent urticarial rash, malaise, weight loss, night sweats, headaches and bone pains. Initial investigations indicated an elevated erythrocyte sedimentation rate, white cell count and a monoclonal immunoglobulin-M paraprotein. Histological examination revealed a perivascular mixed inflammatory infiltrate with leukocytoclasis, nuclear dust without fibrinoid necrosis and extravasated red blood cells. A diagnosis of Schnitzler's syndrome was made. Over an 8-year period, the patient was treated with continuous oral prednisone (minimum dose 20 mg/day) combined with multiple systemic agents. He was commenced on anakinra, a recombinant form of human interleukin-1 receptor antagonist, at a dose of 100 mg injected subcutaneously daily. On review 1 week later, the patient's systemic symptoms had resolved, and his previously elevated white cell count and inflammatory markers had normalized. The use of anakinra in our patient resulted in resolution of symptoms and has enabled cessation of oral prednisone. Our patient remains symptom free on anakinra after 14 months of follow up.

The list of multisystem diseases involving both kidney and skin is long and includes immunologic disorders like systemic lupus erythematodes, a broad variety of vasculitides, metabolic disorders like diabetes mellitus, and infectious diseases. The present work describes the first case of renal failure due to Schnitzler's syndrome, a rare entity characterized by the association of generalized chronic urticaria, monoclonal IgM gammopathy, and osteosclerotic lesions. The described patient experiences improvement of renal function after treatment with the chimeric anti-CD20 antibody rituximab, indicating that the impairment of renal function might be mediated by B-lymphocytes. Renal insufficiency is known to be a potential complication of hypocomplementemic urticarial vasculitis. The present case reveals that it can occur in normocomplementemic urticarial vasculitides as well. Schnitzler's syndrome is a rare but probably underdiagnosed syndrome. It should be considered in the differential diagnosis of rash and coincidental renal failure of unknown origin. Immunofixation of immunoglobulins constitutes the crucial diagnostic step, since monoclonal gammopathy is a constant clinical sign in this entity.

Schnitzler's syndrome is a rare condition with chronic urticaria, intermittent fever, bone pain, and a monoclonal IgM gammopathy. Most patients have a chronic and indolent course, but a small number ultimately progress to a lymphoplasmacytic malignancy. We describe a patient with Schnitzler's syndrome who entered an accelerated phase of clinical deterioration with repeated thromboses of the cerebral and coronary arteries that ultimately led to a fatal outcome. We found that the he fulfilled the Sapporo criteria for definite antiphospholipid syndrome and had elevated blood levels of homocysteine during the active clotting phase of the disease. We suggest that the association with immune-mediated or metabolic disorders, such as the antiphospholipid syndrome and hyperhomocysteinemia, may unfavorably affect the otherwise chronic and stable course of patients with Schnitzler's syndrome. The systemic clotting disorder, the association with the antiphospholipid syndrome and hyperhomocysteinemia, and the biclonal rather than monoclonal IgM gammopathy were striking features of this atypical case of Schnitzler's syndrome.

Background: Schnitzler's syndrome is a rare etiology of chronic urticaria. The disease is characterized by the association of chronic urticaria, intermittent chronic fever, bone pain, osteosclerotic bone lesions and IgM monoclonal gammapathy. More than fifty patients with this syndrome have been reported since Schnitzler reported the first case in 1974, but neuropathies are seen only in a few cases., Case Report: Our patient developed, eight years after the diagnosis of Schnitzler'syndrome, a peripheral sensitive neuropathy. Anti-myelin-associated glycoprotein antibodies were not significant. A nerve biopsy specimen has revealed aspecific demyelinization. Direct and indirect immunofluorescence were negative. We conclused is that our patient presented chronic inflammatory demyelinating polyneuropathy., Discussion: We found one published case of Schnitzler's syndrome and myelin-associated glycoprotein reactive peripheral neuropathy. The diagnosis of chronic inflammatory demyelinating polyneuropathy is a diagnosis of elimination. It is not the most common neuropathy associated with monoclonal gammapathy. To the best of our knowledge, it is the first case of Schnitzler's syndrome with this type of neuropathy. But there are some descriptions of chronic inflammatory demyelinating polyneuropathy presenting autoantibody activity against a myelin component, up to two years after the diagnosis of IgM monoclonal gammapathy.

A seventy-year-old man with a variant type of Schnitzler's syndrome is reported. Physical examination showed pruritic urticarial lesions on the extremities, arthralgia of knee joints, and intermittent fever. Laboratory investigations revealed a high level of IgG, an increased enythrocyte sedimentation rate, urinary Bence-Jones protein, and an M-bow in serum protein electrophoresis, which was shown to be a monoclonal IgG kappa type. Histological examination showed perivascular neutrophil and lymphocytic infiltration into the upper dermis and diffuse neutrophilic infiltration in the middle dermis. One of the clinical features of typical Schnitzler's syndrome is IgM macroglobulinemia, and this is a very rare case of this syndrome with IgG gammopathy.

Schnitzler's syndrome (SS) is characterized by the association of generalized chronic urticaria, osteocondensation and monoclonal IgM gammopathy. Nonsteroidal anti-inflammatory drugs and systemic steroids are the most promising treatments. In our patient, they were ineffective. By contrast, during the follow-up period of 18 months, interferon alpha(2b) therapy (IFN-alpha) relieved the patient from its urticarial lesions and bone pain. IFN-alpha was tried to be stopped twice: each time, relapse of urticaria was noticed and, each time, the cutaneous lesions disappeared after IFN-alpha had been reintroduced. Furthermore, our observation supports the idea of the interleukin (IL)-1-mediated pathogenesis of SS as IFN-alpha induces high levels of IL-1 receptor antagonists. IFN-alpha could be an alternative treatment in disabling SS resisting other drugs., (Copyright 2002 S. Karger AG, Basel)