Human herpesvirus 8 (HHV-8) infection is associated with Kaposi's sarcoma, primary effusion lymphomas and HIV-1-associated multicentric Castleman's disease (Cesarman & Knowles, 1997). A PCR-based study also suggested an association between HHV-8 and multiple myeloma which could not be confirmed using anti-HHV-8 antibody detection (Rettig et al, 1997; Marcelin et al, 1997). The POEMS syndrome is a rare multisystem disorder characterized by the association of polyneuropathy, organomegaly, endocrinopathy of various forms, monoclonal immunoglobulin component in serum and skin changes (Soubrier et al, 1994). The histological hallmarks of POEMS syndrome are osteosclerotic myeloma in bone and plasmacytic multicentric Castleman's disease in lymph nodes. We retrospectively looked for antibodies to HHV-8 in 13 patients with POEMS syndrome (Soubrier et al, 1994). All patients (four female, nine male; aged 55 ± 10 years) had polyneuropathy meeting the criteria for chronic demyelinating neuropathy, endocrinopathy, skin changes, and a monoclonal component containing lambda light chain in serum. Osteosclerotic bone lesions were disclosed in seven patients. We also tested 10 patients with classic Kaposi's sarcoma as positive controls. Immunofluorescence assay was done on PEL cell line latently infected with HHV-8 but not with Epstein-Barr virus (BCP-1, provided by P. S. Moore, New York, U.S.A.) (Simpson et al, 1996). HHV-8 antibodies could be detected in only one out of 13 patients with POEMS syndrome and 10/10 Kaposi's controls. The 57-year-old female patient with POEMS syndrome and anti-HHV-8 antibodies in serum had peripheral lymphadenopathy with features of Castleman's disease. Among the 12 POEMS syndrome patients with no detectable anti-HHV8 antibodies in serum, four also had Castleman's disease proven by lymph node or spleen biopsy. None of the five patients with POEMS syndrome and Castleman's disease had HIV infection. Because multicentric Castleman's disease is a distinctive feature of the POEMS syndrome, HHV-8 was a strong candidate for aetiopathogenesis in this syndrome. Moreover, the HHV-8 genome contains numerous open reading frames with homology to known cellular genes, including a viral IL-6 which is functionally active on human myeloma cells (Burger et al, 1998). Interestingly, overproduction of proinflammatory cytokines (tumour necrosis factor-alpha, IL-1-beta, IL-6) and vascular endothelial growth factor has been demonstrated in POEMS syndrome (Soubrier et al, 1997). Unlike other human herpesviruses, with the exception of herpes simplex virus type 2, infection with HHV-8 is not widespread. On the basis of antibody reactivity, HHV-8 seroprevalence is estimated at about 5% in the U.K., 10–35% in Mediterranean countries and up to 25% in the U.S.A. (Simpson et al, 1996). Hence, HHV-8 seroprevalence in POEMS syndrome (7.6%) does not seem to differ from the general population. One could argue that serological testing provides only indirect evidence for HHV-8 infection. Serological data on HHV-8 infection have been shown to correlate reliably with virus detection by PCR or Southern blot hybridization in Kaposi's sarcoma, body-cavity based lymphomas and HIV-related Castleman's disease lesions (Cesarman & Knowles, 1997). Of note, HHV-8 infection of bone marrow dendritic cells, which has been claimed to occur in multiple myeloma, could not be corroborated by serological testing and was not confirmed by other groups using highly sensitive PCR methods (Rettig et al, 1997; Marcelin et al, 1997; Cull et al, 1998). In conclusion, HHV-8 infection does not appear to relate to Castleman's disease in the setting of POEMS syndrome.
Objective To clarify sex differences in early axial spondyloarthritis (SpA). Methods In total, 475 patients included in the Devenir des Spondylarthropathies Indifférenciées Récentes (Outcome of Recent Undifferentiated Spondylarthropathies) cohort, a prospective multicenter French cohort of patients with early inflammatory back pain suggestive of SpA, and fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA were studied. The clinical and imaging features were compared between sexes and according to the clinical or imaging arm of the ASAS criteria using univariate and multivariate analysis. Results Comparisons between the 239 men and 236 women showed that women had higher disease activity when measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Patient Global Score and higher fatigue and functional scores despite having less radiographic sacroiliitis and magnetic resonance imaging (MRI) inflammation of sacroiliac joints and the spine than men. Disease activity measured by the C‐reactive protein (CRP)–based Ankylosing Spondylitis Disease Activity Score was not different between men and women. In contrast to patients classified with the clinical arm, disease activity and functional scores did not differ between women and men with sacroiliitis on imaging scans, except for fatigue and the Ankylosing Spondylitis Quality of Life questionnaire. Women with sacroiliitis had more peripheral involvement and more family history, whereas HLA–B27 positivity, elevated CRP, and MRI inflammation of the spine were associated with male sex. Conclusion Women with early axial SpA according to the ASAS criteria had greater disease activity when measured by the BASDAI and worse functioning despite fewer radiologic abnormalities than men. The differences in disease expression may be confounding factors to establish the diagnosis of SpA and to assess disease activity in women, suggesting that the imaging arm is a pivotal measure in the ASAS criteria.
Objective To develop and validate a patient knowledge questionnaire regarding axial spondyloarthritis (axSpA). Methods Knowledge considered essential for patients with axSpA was identified through Delphi rounds among rheumatologists, healthcare professionals (HCPs), and patients, then reformulated to develop the knowledge questionnaire. Cross-sectional validation was performed in 14 rheumatology departments to assess internal validity (Kuder-Richardson coefficient), external validity, acceptability, reproducibility (Lin concordance correlation coefficient), and sensitivity to change (knowledge score before vs after patient education sessions and effect size). Results The Spondyloarthritis Knowledge Questionnaire (SPAKE) is a self-administered 42-item questionnaire with a 32-item short form, both scored 0 to 100, assessing knowledge of disease, comorbidities, pharmacological treatments, nonpharmacological treatments, self-care, and adaptive skills. In the validation study (130 patients; 67 [51.5%] male, mean age 43.5 [SD 12.9] yrs), the mean (SD) score of the long-form questionnaire was 71.6 (15.4), with higher scores (better knowledge) in nonpharmacological treatments and adaptive skills and lower scores in cardiovascular comorbidity and pharmacological treatments. Acceptability was good, with no missing data; the internal validity coefficient was 0.85. Reproducibility was good (0.81, 95% CI 0.72-0.89). SPAKE showed good sensitivity to change; scores were 69.2 (15.3) then 82.7 (14.0) after patient education sessions (Hedges effect size = 0.92, 95% CI 0.52-1.31). Conclusion SPAKE is a knowledge questionnaire for patients with axSpA, developed with the involvement of HCPs and patients and reflecting current recommendations for the management of axSpA. SPAKE will be useful in assessing knowledge acquisition and self-management strategies in routine care and research.
To describe the prevalence of fibromyalgia (FM) in an axial spondyloarthritis (axSpA) population and to confirm that concomitant FM had a negative impact on tumour necrosis factor blockers' (TNFb) response.Prospective observational study with two visits 3 months apart.Adult patients with AxSpa initiating a TNFb.FM was defined by the Fibromyalgia Rapid Screening Tool (FiRST) at baseline and also by a sustained positive FiRST (both visits) and by a fulfilment of the 1990 American College of Rheumatology criteria for FM.Prevalence of FM; evaluation of the impact of a concomitant FM on TNFb response (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50) as primary endpoint), adjusted by factors known to have an impact on TNFb response.Among the 508 patients included in the main analysis, 192 (37.8%) were screened at baseline as FM. Percentage of success after 12 weeks of treatment was lower in the FM group for most of the effectiveness endpoints (eg, BASDAI 50: 45.3% vs 54.1% in the FM/not FM groups according to the FiRST), except for the C reactive protein change endpoints which were not different across groups.This study confirms that FM coexists in patients with axSpA and that its presence seems to have a negative impact on TNFb response, which seems more related to the self-reported instruments used in its evaluation, rather than a different treatment effect of the molecule in this subgroup of patients.
Monoclonal gammopathy of renal significance (MGRS) can manifest in many different ways depending on the nature of the immunoglobulin and its physicochemical properties. MGRS can lead to the discovery of a hematological malignancy. We report the case of a 32-year-old female patient who underwent renal biopsy on account of an impure nephrotic syndrome associated with immunoglobulin (Ig)G κ monoclonal gammopathy. Histological analysis revealed membranoproliferative glomerulonephritis with IgG, IgM, κ, λ, and C3 deposits. Due to an unfavorable progression, a second renal biopsy was performed. Electron microscopy analysis revealed an immunotactoid glomerulopathy. At the same time, a POEMS syndrome diagnosis (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin abnormalities) was confirmed in light of the following: 1) IgG κ monoclonal gammopathy, 2) axonal neuropathy, 3) osteosclerosis, 4) melanoderma, 5) hepatosplenomegaly and adenopathies, 6) Castleman disease, and 7) edema. Our observation is the first case of immunotactoid glomerulopathy leading to the discovery of a POEMS syndrome. Renal involvement in POEMS syndrome typically exhibits a thrombotic microangiopathy-like membranoproliferative glomerulonephritis appearance associated with endothelial lesions stigmata. However, monoclonal immunoglobulin deposition disorder should be considered in the event of an atypical case. In this indication, electron microscopy is the examination of choice for assessing immunoglobulin deposition nephropathy. .
Spondyloarthritis (SpA) and Takayasu arteritis (TA) are two chronic inflammatory diseases; their association is rare but has already been described in the literature.
Objectives
The aim of this study was to describe the clinical features of patients suffering from SpA associated with TA and to identify some characteristics of SpA patients that could be suggestive of TA. Finally, we analyzed treatments that were generally used in this clinical context and their efficacy in TA.
Methods
This retrospective study collected patients9 cases from 10 medical centers in France. Data collection relied on a call for observations on behalf of the Club Rhumatismes et Inflammation. A standardized questionnaire was established and validated by the investigators.
Results
We included 14 patients, 10 of them were women. The median age at SpA diagnosis was 43.5 years (ranging from 19 to 63). Subtypes of SpA were: ankylosing spondylitis (n=11), psoriatic arthritis (n=2) and SAPHO syndrome (n=1). HLA-B27 was positive in 3 cases, negative in 9 cases and unknown in 2 cases. SpA was diagnosed before TA in 13 cases (median time of 4.5 years). During SpA patients9 follow-up, TA revealing symptoms were: clinical detection of a pulse diminution/abolition (3/14), superior limb claudication (2/14), and vascular sound (2/14). Other TA diagnoses were made by the exploration of inflammatory cervical pain (1/14), or the radiological detection of radial artery thrombosis (1/14). TA was confirmed by CT (11/14) and/or PET (6/14) or anatomopathology (1/14). Laboratory tests shown increased acute phase reactants in all cases, C-reactive protein being ≥25mg/L in 71% of the cases; systemic inflammation was the revealing factor for TA in 6 cases. Seven patients were treated with anti-TNF: 2 with adalimumab, 4 with etanercept (among whom one required a switch to infliximab and another required a switch to adalimumab, and then to golimumab) and 1 with infliximab. Anti-TNF treatment was introduced in 5/7 cases after TA diagnosis. Vascular surgery was necessary for 4 patients.
Conclusions
Association of SpA and TA is probably not coincidental. The recent findings of double negative T cells expressing IL-23 receptor in the aorta of mice presenting with a model of SpA supports this association[1]. The careful peripheral pulse palpation and vessels auscultation should be systematic and stay the first alert to TA diagnosis in SpA patients. Moreover, increased acute phase reactants during SpA follow-up, without alternative explanation, should alert physicians and lead to screen patients for TA, as well as for an inflammatory bowel disease. Finally, the identification of this association has therapeutic implications since anti-TNF alpha have already demonstrated their efficacy in both diseases as observed in our study.
References
Sherlock et al., IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+CD4−CD8− entheseal resident T cells.
