Risk factors for hydroxychloroquine retinopathy in systemic lupus erythematosus: a case-control study with hydroxychloroquine blood-level analysis.

OBJECTIVE: HCQ is an essential medication in SLE, proven to lengthen survival and reduce flares. Its use, however, is limited by its rare but severe ophthalmological complications. Here, we aimed to analyse factors associated with HCQ retinopathy including HCQ blood levels. METHODS: This case-control study compared SLE patients with and without HCQ retinopathy, defined by abnormal results for at least two of the following ophthalmological tests: automated visual fields, spectral-domain optical coherence tomography (SD-OCT), multifocal electroretinogram (mfERG) and fundus autofluorescence. We compared clinical and laboratory findings to assess risk factors for HCQ retinopathy. RESULTS: The study included 23 patients with confirmed retinopathy (cases) and 547 controls. In the univariate analysis, age (P < 0.001), height (P = 0.045), creatinine clearance (P < 0.001), haemoglobin concentration (P = 0.01), duration of HCQ intake, (P < 0.001), higher cumulative HCQ dose (P < 0.001) and geographical origin (West Indies and sub-Saharan Africa) (P = 0.007) were associated with the risk of retinopathy, while HCQ blood levels were not. In the multivariate analysis, only cumulative dose (P = 0.016), duration of intake (P = 0.039), creatinine clearance (P = 0.002) and geographical origin (P < 0.0001, odds ratio 8.7) remained significantly associated with retinopathy. CONCLUSION: SLE patients on HCQ should be closely monitored for retinopathy, especially those from the West Indies or sub-Saharan Africa, or with renal insufficiency, longer HCQ intake or a high cumulative dose. Although reducing the daily dose of HCQ in patients with persistently high HCQ blood levels seems logical, these concentrations were not associated with retinopathy in this study with controls adherent to treatment.

Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study).

INTRODUCTION: Hydroxychloroquine (HCQ) is an important medication for treating systemic lupus erythematosus (SLE). Its blood concentration ([HCQ]) varies widely between patients and is a marker and predictor of SLE flares. This prospective randomised, double-blind, placebo-controlled, multicentre study sought to compare standard and adjusted HCQ dosing schedules that target [HCQ] ≥1000 ng/ml to reduce SLE flares. PATIENTS AND METHODS: [HCQ] was measured in 573 patients with SLE (stable disease and SELENA-SLEDAI≤12) treated with HCQ for at least 6 months. Patients with [HCQ] from 100 to 750 ng/ml were randomised to one of two treatment groups: no daily dose change (group 1) or increased HCQ dose to achieve the target [HCQ] (group 2). The primary end point was the number of patients with flares during 7 months of follow-up. RESULTS: Overall, mean [HCQ] was 918±451 ng/ml. Active SLE was less prevalent in patients with higher [HCQ]. A total of 171 patients were randomised and followed for 7 months. SLE flare rates were similar in the two groups (25% in group 1 vs 27.6% in group 2; p=0.7), but a significant spontaneous increase in [HCQ] in both groups between inclusion and randomisation strongly suggested improved treatment adherence. Patients at the therapeutic target throughout follow-up tended to have fewer flares than those with low [HCQ] (20.5% vs 35.1%, p=0.12). CONCLUSIONS: Although low [HCQ] is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up.

[Pregnancy in dermatomyositis and polymyositis]. / Grossesse au cours des dermatomyosites et polymyosites.

AIM: To determine the incidence of pregnancies during the inflammatory myopathy (IM), its influence on this disease and the influence of IM on the pregnancy's outcome. METHODS: From 1979 to 2007 we have collected retrospectively 67cases of IM (53 women and 14 men) in the department of internal medicine CHU Hedi Chaker of Sfax (Tunisia). Diagnosis criteria were those and Peter. We have included pregnancies occurring after diagnosis of DM or PM and cases of IM occurring during pregnancy or postpartum. RESULTS: Five women (4DM and PM), average age 30.6 years (range 26 - 41 years) conducted 10 pregnancies (9.4%). The fertility rate is 2 pregnancies per patient. Nine pregnancies occurred after the diagnosis of myositis in 4 women. IM was inactive at conception in all this cas.No flare-up in IM has been noted during these pregnancies. The DM was revealed to the 10th day post-partum in one patient. Therapeutic interruption of pregnancy was needed in 3 cases. 4 pregnancies were completed without incident and resulted in the birth of healthy newborns. Foetal complications were observed in the other two pregnancies occurring in one patient who also presents an APS associated with DM. It was a foetal death in utero and premature delivery of a newborn who died in 3rd day after birth. CONCLUSION: Pregnancy in the MI is rare. Its influence on the activity of the disease is variable, both during the pregnancy than postpartum. The foetal prognosis is good when the the disease is in remission. However foetal complications are important in case of active IM.

Health Outcomes of 215 Mothers of Children With Autoimmune Congenital Heart Block: Analysis of the French Neonatal Lupus Syndrome Registry.

OBJECTIVE: Transplacental passage of maternal anti-SSA and anti-SSB antibodies, potentially associated with maternal autoimmune diseases, can cause neonatal lupus syndrome. Given the paucity of data in this setting, we report short- and long-term outcomes of mothers of offspring with congenital heart block (CHB). METHODS: This retrospective study included anti-SSA/SSB antibody-positive mothers of fetuses with high-degree CHB and focused on their health status before pregnancy, at CHB diagnosis, and thereafter. RESULTS: We analyzed 215 women with at least 1 pregnancy with CHB. Prior to this diagnosis, only 52 (24%) mothers had been diagnosed with an autoimmune disease, mainly systemic lupus erythematosus (SLE; n = 26, 12%) and Sjögren syndrome (SS; n = 16, 7%). Six more were diagnosed with an autoimmune disease during the index pregnancy. Of the 157 mothers (73%) with no such diagnosis at childbirth, 77 (49%) developed one after a median follow-up of 11 years (range: 21 days to 54 years). By the end of follow-up, 135 women (63%) had an autoimmune disease diagnosis, mainly SLE (n = 54, 25%) and SS (n = 72, 33%). Three patients with SLE had renal involvement, and only 6 (3%) had required an immunosuppressive drug at any point. The symptoms best predicting autoimmune disease development were arthralgia and myalgia (P < 0.001), dry syndrome (P = 0.01), and parotid swelling (P = 0.05). CONCLUSION: One-quarter of the patients had an autoimmune disease diagnosis at the time of the fetal CHB diagnosis. Nearly half of those without an initial diagnosis progressed during follow-up, most without severe manifestations. Severe diseases such as lupus nephritis were rarely seen, and immunosuppressive drugs were rarely required.

Retrospective study of elderly onset sarcoidosis in Tunisian patients.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown etiology. It affects mostly young adults. In the elderly, the presentation of this disease is different, often posing positive diagnosis problems. OBJECTIVES: We intend to describe the various clinical features and the management of sarcoidosis in elderly patients (age ≥65 years) compared to the younger ones. METHODS: We performed a retrospective, descriptive and comparative study in the Department of Internal Medicine in the University Hospital Hedi Chaker, Sfax, Tunisia, between 1996 and 2016. RESULTS: From a series of 80 patients, we found sixteen patients (20%) with sarcoidosis diagnosed after the age of 65 years. A female preponderance (81,25%) was noted. Intrathoracic involvement concerned 13 patients (81,3%). Extrapulmonary signs were also frequent (93,8%). The main extrathoracic manifestations were ganglionar involvement (75%), an alteration of the general health (31,3%), hepatic involvement (31,3%), cutaneous involvement (25%) and ocular involvement (25%). Biological manifestations were hypercalcemia, hypercalciuria, lymphopenia and hypergammaglobulinemia noted in respectively 12,5%, 12,5%, 31,3% and 50% of the cases. Angiotensin-converting enzyme(ACE) level was elevated in 100% of the patients. Lymphadenopathy and cutaneous biopsies were important contributing factors to diagnosis (respectively: 100% and 75% were positive). Oral corticosteroid therapy was required in 50% of cases. Evolution was marked by pulmonary fibrosis in two cases. Satisfactory course of the disease was observed in the other patients. CONCLUSION: Young and elderly subjects had common characteristics of sarcoidosis, except for more coexisting chronic morbidities, no erythema nodosum and more frequent high levels of ACE in the elderly group.

Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence.

BACKGROUND: Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients. METHODS: HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ < 200 ng/mL. RESULTS: The mean (± SD) HCQ levels were 469 ± 223 ng/mL in serum and 916 ± 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 ± 0.15. In the multivariate analysis, low whole-blood HCQ levels (P = 0.023), but not serum HCQ levels, were independently associated with active SLE. From the mean serum/whole-blood level ratio, a serum HCQ level of 106 ng/mL was extrapolated as the corresponding cut-off to identify non-adherent patients with a sensitivity of 0.87 (95% CI 0.76-0.94) and specificity of 0.89 (95% CI 0.72-0.98). All serum HCQ levels of patients with whole-blood HCQ below the detectable level (< 20 ng/mL) were also undetectable (< 20 ng/mL). CONCLUSIONS: These data suggest that whole blood is better than serum for assessing the pharmacokinetic/pharmacodynamic relation of HCQ. Our results support the use of serum HCQ levels to assess non-adherence when whole blood is unavailable.

Clinical and diagnostic value of ribosomal P autoantibodies in systemic lupus erythematosus.

OBJECTIVE: To analyse prospectively the diagnostic sensitivity and specificity as well as the clinical relevance of ribosomal P (anti-P) autoantibodies in a large cohort of SLE patients. METHODS: The anti-P autoantibodies were evaluated in the serum of 200 Tunisian SLE patients at disease onset and 130 various control subjects by a sensitive immunodot assay. A complete laboratory evaluation and clinical examination were performed in each SLE patient. During the follow-up, the patients were regularly monitored for clinical parameters. Global SLE activity was measured by the ECLAM. RESULTS: The sensitivity and specificity of anti-P testing for SLE were 23.5 and 98.4%, respectively. The anti-P-positive samples 14/47 (29.8%), 27/47 (57.4%) and 5/47 (10.6%) were negative for anti-dsDNA, anti-Sm or both antibodies, respectively. The anti-P-positive patients showed more active disease activity and a much higher prevalence of arthritis. An association between IgG aCLs and anti-P antibodies was also found. However, anti-P antibodies were not associated with neuropsychiatric manifestations or lupus nephritis. CONCLUSION: This study does not seem to confirm the described association of anti-P antibodies with neuropsychiatric manifestations of SLE. However, it supports the anti-P antibody association with arthritis and disease activity as well as the presence of aCL. Based on our study and other related studies, we propose that, akin to anti-Sm and anti-dsDNA, anti-P antibodies detected by one agreed method may be considered for inclusion as a criterion for the classification of SLE.

Adult Still's disease and squamous cell carcinoma in a 69-year-old woman.

Adult-onset Still's disease (AOSD) has been recognized as a cause of fevers of unknown origin. Malignancies are the most important differential diagnoses of AOSD which has been rarely reported in association with cancer. The present paper undertakes the study of a 69-year-old Tunisian woman with AOSD according to the diagnostic criteria of Yamaguchi. She was treated by prednisone, then associated with methotrexate. 18 months later, she developed a squamous cell carcinoma treated with chemotherapy and radiotherapy.

Clinical and serological profile of systemic sclerosis in Tunisia: A retrospective observational study.

OBJECTIVE: The Prevalence of systemic sclerosis (SSc) and different clinical subsets varies across the world. Few data have been published on SSc patients in North Africa. Our objective was to describe a SSc cohort in south of Tunisia and to compare clinical findings, disease subsets and antibodies with other international SSc populations. METHODS: In this retrospective observational study, Folders of patients with SSc seen in the internal medicine section of the Hedi Chaker Hospital between 2000 and 2013 were retrospectively analyzed. The diagnosis of SSc was retained according to ACR/EULAR 2013 criteria. Patients were classified into diffuse cutaneous SSc and limited cutaneous SSc subsets. Comparison with other cohorts was made based on published information. RESULTS: A higher female: male ratio (8:1) and a higher diffuse subset prevalence (82%) was found in this Tunisian cohort comparing with others. We also found a lower prevalence of calcinosis and anticentromere antibodies. Within each subset, diffuse cutaneous and limited cutaneous scleroderma clinical findings were similar with other systemic sclerosis populations except for a very low prevalence in renal crisis and pulmonary hypertension. Our results indicate overlap syndrome defined as scleroderma associated with others connective tissue disorder's is a relatively common condition. CONCLUSION: With slight variations, perhaps due to genetic, environmental or referral factors, SSc in this cohort appears to be similar to that described in other part of the world.

[Henoch-Shonlein purpura in adults in South Tunisia: a series of 14 cases]. / Purpura rhumatoïde de l'adulte dans le sud tunisien: une série de 14 cas.

Henoch-Schonlein purpura (HSP) is a small-vessel vasculitis secondary to IgA deposits. We conducted a retrospective study of 14 cases of HSP in adults based on EULAR/PRINTO/PRES classification criteria for HSP over a period of 18 years (1996 to 2014) in Department of Internal Medicine at the Hedi Chaker University Hospital, Sfax, South Tunisia. The purpose of our study was to highlight the epidemiological, clinical, therapeutic and evolutionary features of HSP in our adult patients. The average age of patients was 33 years (ranging from 17-64 years) with male predominance (sex ratio of 1.8). Vascular purpura with petechiae was constant. Articular manifestations (arthralgia and/or arthritis) were reported in 9 patients (64.2%). Gastrointestinal involvement was reported in 13 patients (92.8%). Renal failure was found in 11 patients (78.5%) revealed by nephrotic proteinuria in 7 cases, microscopic haematuria in 9 cases, high blood pressure in 4 cases and renal impairment in 1 case. The most common histological type was diffuse proliferative endocapillary glomerulonephritis (36.3%). High dose corticotherapy was initiated in 7 patients with proliferative renal impairment, bolus of Solu-Medrol in 4 cases, associated with cyclophosphamide in one case. Two patients with severe gastrointestinal involvement received corticotherapy. After a mean follow-up period of 18.5 months (4-36 months), outcome was favorable in all cases without relapse and chronic renal failure was reported only in one case.

Malignancy in a retrospective cohort of 17 patients with Dermatomyositis or Polymyositis in southern Tunisia.

INTRODUCTION: The prognosis of dermatomyositis (DM)/ polymyositis (PM) in adults is partly related to their association with neoplasia. The aim of our study was to report the epidemiologic, clinical, paraclinical, therapeutic and evolutionary aspects of DM associated with malignancy in patients from Sfax, south eastern of Tunisia. METHODS: A retrospective cohort study of patients with DM or PM admitted in Dermatology and Internal Medicine Departments of Hedi Chaker University Hospital of Sfax between 1996 and 2015. Cases of DM or PM associated with malignancy were retained. RESULTS: Seventeen cases (13.5%) of DM or PM associated with malignancy were noted. Fourteen patients had DM and 3 patients had PM. The Sex ratio M / F was 0.3 and the mean age at diagnosis was 56.5 years. In DM patients, malignancy preceded the myositis in 64.2% of cases. In PM patients, only one patient was known to have breast cancer and the myositis revealed the cancer for 2 others. Treatment consisted of corticosteroids associated with methotrexate in 4 cases. Outcome was fatal in 5 cases (29.4%), due to the underlying cancer in 3 cases. Swallowing disorders related to DM/PM were responsible for death in 2 cases. CONCLUSION: There are no specific clinical or biological features in paraneoplastic DM. In our series, breast neoplasm represented the first cancer associated with DM. Cancers of nasopharynx, colon and urinary tract had the second position.

A challenging entity: multiple sclerosis or collagen tissue disorders: A case series of 6 patients.

BACKGROUND: Multiple sclerosis and other demyelinating processes are sometimes difficult to differentiate from the neurological involvement in autoimmune diseases. Distinguishing multiple sclerosis from other lesions due to autoimmune diseases is crucial to avoid unsuitable or delayed treatments. METHODS: Charts of 6 patients diagnosed with mimicking multiple sclerosis between 1996 and 2014 were retrospectively assessed. RESULTS: The mean age at diagnosis was 35±7 years. The most commonly neurological manifestation at onset was paraparesis due to transverse myelopathy and uni/bilateral optic neuropathy. All our patients suffered from recurrent episodes of optic neuritis with a mean lag time of 12 months. Other initial presenting neurological manifestations in our patients included ataxic gait and pyramidal syndrome. Systemic symptoms occurred a long time before or after their initial neurological presentation. All patients had numerous T2 hyperintense lesions in the periventricular white matter and spinal cord with contrast enhancement. The antibodies tests revealed the presence of significant amounts of anti-nuclear antibodies. The anti-phospholipid antibodies were negative in all patients. All patients were treated with corticosteroid therapy and neurological features were cleared in all cases. CONCLUSION: Multiple sclerosis, other myelitis and optic neuritis, are sometimes difficult to differentiate from CNS involvement in autoimmune disease. Indeed, the clinical presentation, immunological profile and MRI lesions may be similar.

[Liver involvement in Rendu-Osler disease: a case report and review of literature]. / Atteinte hépatique au cours de la maladie de Rendu-Osler: à propos d'un cas et revue de la littérature.

A 48 years-old-woman was admitted for anectric cholestasis. A history of recurrent personal and familial epistaxis was noted. Biologic findings revealed iron deficiency anemia and moderate cholestasis. Viral serologic tests, antimitochondrie and anti smooth muscle antibodies were negative. Abdominal tomography showed multiple arterio-venous shunts of the liver. The diagnosis of liver involvement due to Rendu Osler disease was made. Treatment with oral ferrous iron of 150 mg/day was administered and regular biological and morphologic controls of liver was decided.

Late-onset primary antiphospholipid syndrome in the elderly: a report of seven cases.

AIM: We describe the clinical profile of elderly with primary antiphospholipid syndrome (APS). METHODS: Charts of seven elderly patients diagnosed with APS between 1996 and 2012 were retrospectively assessed. RESULTS: The mean age at diagnosis was 77 ± 6 years (67-84 years). Two patients had experienced frequent miscarriages. Five patients presented with deep venous thrombosis of the lower limb, one had venous thrombosis of the upper limb and brachiocephalic vein and another had a cerebral ischemic stroke. The antiphospholipid antibodies tests revealed the presence of significant amounts of anticardiolipin antibodies, 12 weeks apart, twice in four patients. The antibodies to ß2-glycoprotein 1 were positive twice in two patients and lupus anticoagulant in one of these. All patients were treated with heparin and long-term anti-vitamin K and thrombosis was cleared in all cases. Two patients presented with bleeding complications: hematuria and hematoma of the buttock in one patient and rectal bleeding in another case. Two elderly developed a colon cancer and lymphoma 1 year later. CONCLUSION: In this report, we report on primary APS in the elderly, to discuss its prevalence and the clinical significance of positive antiphospholipid antibodies in subjects over the age of 65 years.

A Critical Review of the Effects of Hydroxychloroquine and Chloroquine on the Eye.

Hydroxychloroquine (HCQ) and chloroquine have been used for more than 50 years to treat systemic lupus erythematosus (SLE) and other rheumatic diseases. In general, these drugs are well tolerated and rarely need to be discontinued because of an adverse systemic reaction. However, both medications can be irreversibly toxic to the retina. A new study indicates that toxicity is not as rare as once believed, but depends critically on daily dosage and duration of use, as well as other risk factors. With attention to dosage and other factors, and with proper screening for early signs of toxicity, HCQ can be prescribed with relative safety even over long periods of time.

Acute generalized exanthematous pustulosis induced by piroxicam: a case report.

Acute generalized exanthematous pustulosis (AGEP) is a severe adverse cutaneous reaction characterized by an acute episode of sterile pustules over erythematous-edematous skin. The main triggering drugs are antibiotics, mainly beta-lactam and macrolides. Non-steroid anti-inflammatory drugs may rarely be responsible. We describe a case of a woman with AGEP, who presented with generalized pustulosis lesions after the use of piroxicam for renal colic. The diagnosis was confirmed by the clinical and histological correlations and the dermatosis resolved after withdrawal of the drug.

Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up.

OBJECTIVES: Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups. METHODS: Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361). RESULTS: The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D <10 ng/mL) was observed in 27 (15.9%), insufficiency (10≤25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D≥30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22). CONCLUSIONS: We found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate.

Hydroxychloroquine-induced pigmentation in patients with systemic lupus erythematosus: a case-control study.

IMPORTANCE: Hydroxychloroquine-induced pigmentation is not a rare adverse effect. Our data support the hypothesis that hydroxychloroquine-induced pigmentation is secondary to ecchymosis or bruising. OBJECTIVE: To describe the clinical features and outcome of hydroxychloroquine (HCQ)-induced pigmentation in patients with systemic lupus erythematosus (SLE). DESIGN, SETTING, AND PARTICIPANTS: In a case-control study conducted at a French referral center for SLE and antiphospholipid syndrome, 24 patients with SLE, with a diagnosis of HCQ-induced pigmentation, were compared with 517 SLE controls treated with HCQ. MAIN OUTCOMES AND MEASURES: The primary outcome was the clinical features of HCQ-induced pigmentation. Skin biopsies were performed on 5 patients, both in healthy skin and in the pigmented lesions. The statistical associations of HCQ-induced pigmentation with several variables were calculated using univariate and multivariate analyses. RESULTS: Among the 24 patients, skin pigmentation appeared after a median HCQ treatment duration of 6.1 years (range, 3 months-22 years). Twenty-two patients (92%) reported that the appearance of pigmented lesions was preceded by the occurrence of ecchymotic areas, which gave way to a localized blue-gray or brown pigmentation that persisted. Twenty-three patients (96%) had at least 1 condition predisposing them to easy bruising. Results from skin biopsies performed on 5 patients showed that the median concentration of iron was significantly higher in biopsy specimens of pigmented lesions compared with normal skin (4115 vs 413 nmol/g; P < .001). Using multivariate logistic regression, we found that HCQ-induced pigmentation was independently associated with previous treatment with oral anticoagulants and/or antiplatelet agents and with higher blood HCQ concentration. CONCLUSIONS AND RELEVANCE: Hydroxychloroquine-induced pigmentation is not a rare adverse effect of HCQ. Our data support the hypothesis that HCQ-induced pigmentation is secondary to ecchymosis or bruising.

Coexistence of Behçet's disease with ankylosing spondylitis and familial Mediterranean fever: a rare occurrence.

Behçet's disease (BD) and familial Mediterranean fever (FMF), which are two separate diseases sharing some clinical features, may also coexist in the same patient. Further investigations are needed to understand whether this coexistence is due to either chance or geographical distribution patterns of these diseases or to common etiopathogenetic characteristics. Spondylarthritis as part of the clinical picture in these two diseases has been questioned and probably it is not a prominent characteristic of any of them. We report a 35-year-old Tunisian man who had an association of BD, FMF and Human Leukocyte Antigen (HLA) B27 positive ankylosing spondylitis. Although that spondylarthritis is an infrequent joint involvement of FMF and BD, it must be looked for in case of association of these diseases.

Peripheral neuropathies associated with primary Sjögren syndrome: immunologic profiles of nonataxic sensory neuropathy and sensorimotor neuropathy.

We conducted this study to characterize the relationship between primary Sjögren syndrome (pSS)-associated peripheral neuropathy (PN) and markers of B-cell monoclonal proliferation and chronic activation. The cohort included 120 consecutive patients presenting with definite pSS according to the American-European Consensus Group criteria. Serum markers of chronic B-cell activation included autoantibodies and hypergammaglobulinemia. Markers of monoclonal B-cell proliferation included mixed cryoglobulin, monoclonal gammopathy, abnormal κ/λ free light chain (FLC) ratio, and B-cell non-Hodgkin lymphoma (B-NHL). Definite PN was present in 30 patients (25%) including 7 patients (23%) with sensorimotor neuropathy, 3 patients (10%) with ataxic sensory neuropathy, and 20 patients (67%) with nonataxic sensory neuropathy. Patients with a sensorimotor neuropathy differed from those without PN by higher rates of monoclonal B-cell proliferation markers, that is, mixed cryoglobulin (57% vs. 11%; p = 0.008), monoclonal gammopathy (71% vs. 17%; p = 0.004), higher FLC ratio (2.7 ± 1.5 vs. 1.7 ± 1.8; p = 0.024), and B-NHL (57% vs. 3%; p < 0.001). Patients with nonataxic sensory neuropathy were characterized by a higher age (57.5 ± 10.7 vs. 48.7 ± 14.3 years; p = 0.007), more frequent central nervous system (CNS) involvement (15% vs. 2%; p = 0.04) and a lower prevalence of chronic B-cell activation serum markers, that is, antinuclear antibodies (ANA) (60% vs. 90%; p = 0.003), anti-SSA (Ro) (40% vs. 72%; p = 0.009), anti-SSB (La) (15% vs. 41%; p = 0.039), rheumatoid factor (37% vs. 67%; p = 0.02), and hypergammaglobulinemia (35% vs. 64%; p = 0.023). In multivariate analysis, sensorimotor neuropathy was associated with the presence of B-NHL (odds ratio [OR], 39.0; p < 0.001), whereas nonataxic sensory neuropathy was associated with the presence of CNS involvement (OR, 17.0; p = 0.025) and ANA (OR, 0.07; p < 0.001). In conclusion, we found that up to 25% of pSS patients presented with PN, predominantly sensory neuropathy. Distinctive immunologic profiles were found according to the type of SS-associated neuropathy: nonataxic sensory neuropathy was marked by a low prevalence of B-cell activation markers, and sensorimotor neuropathy was marked by a high prevalence of B-cell monoclonal proliferation markers.