Clinical features and outcomes in patients with human immunodeficiency virus-negative, Castleman disease: a single medical center study in Tunisia.

Introduction: Castleman disease (CD), known as angiofollicular lymph node hyperplasia, is an uncommon condition. The two most common histological subtypes are hyaline vascular and plasma cell. We performed a retrospective analysis to define the clinic-pathological features and survival of CD, which is quite rare focusing on the particularities of our series with a review of the recent literature. Methods: This is a retrospective study conducted in the department of internal medicine of Hedi Chaker hospital in Sfax, Tunisia over 25 years. The disease was histologically confirmed in all patients. For each file, we collected a set of data by filling in a pre-designed form. Results: 18 patients were included. There were 8 men and 10 women with a mean age of 42.8 years. CD was monocentric in 5 cases (28%) and multicentric in 13cases (72%). Clinically, peripheral adenopathy was present in 77.7% of patients and deep adenopathy in 72.2%. Systemic signs were found in 13patients, including general condition (4.4%), fever (16.6%), serositis (27.7%), and skin involvement (33.3%). A biological inflammatory syndrome accompanied the clinical picture in 66% of patients. Abnormalities in the blood count were found in 12cases (66%), with anemia in 11cases, thrombocytosis in 3cases, and hypereosinophilia in 3cases. Cutaneous Kaposi's sarcoma was associated with Castleman's disease in 2cases, Hodgkin's lymphoma, angioimmunoblastic T-cell lymphoma, and lymph node T-cell lymphoma were found in 1case respectively. 3 of the patients had associated connective tissue diseases such as Sjögren's syndrome in 2 cases and rheumatoid arthritis in 1case. HHV8 serology was positive in 1 case with a multicentric plasma cell form. Histologically, the plasma cell form represented 50% of cases, hyaline-vascular (39% of cases), and mixed (11% of cases). Therapeutically, high-dose corticosteroid therapy was initiated in 13 cases. As a second-line treatment, MOPP chemotherapy was used in 1case due to transformation into Hodgkin's lymphoma, and biotherapy (rituximab) was used in 2cases in the multicentric form. Surgical removal of superficial adenopathy was performed in 2patients with monocentric CD. Conclusion : Castleman's disease (CD) is a non-malignant lymphoproliferation of localized or multicentric form with a wide and heterogeneous clinical spectrum. Diagnosis can be difficult due to the lack of clinical and radiological specificity. Management depends on the clinical form involving surgical and/or medical management.

Central retinal vein occlusion : an uncommon complication in sarcoidosis.

Sarcoidosis is a multi-system granulomatosis of unknown etiology, defined by the presence of epithelioid and gigantocellular granulomas, without caseous necrosis. Ocular sarcoidosis manifests mainly as bilateral granulomatous anterior uveitis. Occlusion of the central retinal vein in sarcoidosis is a rare manifestation, which is the particularity of our observation. We report the case of a patient presenting with unilateral central retinal vein occlusion associated with granulomatous anterior uveitis on the same side. Systemic manifestations and further investigations led to the diagnosis of sarcoidosis.

ICOS gene polymorphisms in systemic lupus erythematosus: A case-control study.

The inducible T-cell costimulator (ICOS) may play an important role in adaptive immunity by regulating the interaction between T cells and antigen-presenting cells. Disruption of this molecule can lead to autoimmune diseases, in particular systemic lupus erythematosus (SLE). In this study, we aimed to explore the possible association between ICOS gene polymorphisms and SLE as well as their influence on disease susceptibility and clinical outcomes. A further objective was to assess the potential impact of these polymorphisms on RNA expression. A case-control study, including 151 patients with SLE, and 291 unrelated healthy controls (HC) matched in gender, and geographical origin, was performed to genotype two polymorphisms located in the ICOS gene: rs11889031 (-693 G/A) and rs10932029 (IVS1 + 173 T/C); using the polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The different genotypes were validated by direct sequencing. The expression level of ICOS mRNA was assessed by quantitative PCR in peripheral blood mononuclear cells of SLE patients and HC. The results were analysed using Shesis and spss.20. Our results revealed a significant association between ICOS gene rs11889031 > CC genotype and SLE disease (codominant genetic model 1, (C/C vs. C/T), p = .001, odds ratio [OR] = 2.18 IC [1.36-3.49]); codominant genetic model 2, (C/C vs. T/T) p = .007, OR = 15.29 IC [1.97-118.5]); dominant genetic model, (C/C vs. C/T + T/T) p = .0001, OR = 2.44 IC [1.53-3.9]). Besides, there was a marginal association between rs11889031 > TT genotype and T allele with a protective role from SLE (recessive genetic model, p = .016, OR = 0.08 IC [0.01-0.63] and p = 7.6904E - 05, OR = 0.43 IC = [0.28-0.66], respectively). Moreover, statistical analysis indicated that the rs11889031 > CC genotype was linked with clinical and serological manifestations of SLE, including blood pressure, and anti-SSA antibodies production in SLE patients. However, the ICOS gene rs10932029 polymorphism was not associated with susceptibility to SLE. On the other side, we did not note any effect of the two selected polymorphisms on the level of ICOS mRNA gene expression. The study showed a significant predisposing association of the ICOS rs11889031 > CC genotype with SLE, in contrast to a protective effect of rs11889031 > TT genotype in Tunisian patients. Our results suggest that ICOS rs11889031 may act as a risk factor for SLE and could be used as a genetic susceptibility biomarker.

Granulomatous gingival manifestation in Melkersson Rosenthal syndrome: a case report.

Melkersson-Rosenthal syndrome is a rare condition of unknown etiology. It is characterized by a classical triad of symptoms: relapsing facial and lip swelling, facial palsy and a fissured tongue. We report the case of a 29-year-old female patient who presented with the above-mentioned symptoms of Melkersson-Rosenthal syndrome. However, clinical examination revealed an exceptional manifestation, which is the gingival hyperplasia. The symptoms were partially managed with systemic steroids and surgical resection of gingival hyperplasia. The most significant finding to emerge from our case is that gingival enlargement can be identified as a rare clinical feature of the MRS disease, which is confirmed difficult to be managed.

Acquired hemophilia A in a patient with adult-onset Still's disease: Successful treatment with steroids.

Acquired hemophilia A (AHA) is a potentially life-threatening hemorrhagic disorder with many etiologies. We report the first case in the literature describing the association of AHA with adult-onset Still's disease (AOSD).

Orbital inflammatory pseudotumor revealing multi-organ immunoglobulin G4-related disease.

Relatively recently, the concept that immunoglobulin G4 (IgG4)-related disease is a distinct chronic inflammatory disorder rather than a subset of Sjögren's syndrome has been accepted. IgG4-related disease (IgG4-RD) is a fibro-inflammatory systemic immune-mediated condition that can affect the pancreas, salivary glands, and lymph nodes. Almost every organ may be impacted synchronously or metachronously by this illness, which causes the development of sclerotic masses of varying sizes. Numerous other rheumatic diseases can present with characteristics of IgG4-RD, making it difficult to distinguish between them. However, cases of IgG4-RD involving the bilateral orbits, and pancreas with biological abnormalities are rare. We present a case of an 18-year-old female with vitiligo since the age of 3 years who presented with acute pancreatitis and acalculous cholecystitis, bilateral orbital masses, palpebral edema, and eosinophilia. The patient was diagnosed with IgG4-RD in keeping with clinical presentation and the elevated serum IgG4 level and after elimination of other differential diagnoses. The patient's symptoms gradually relieved after glucocorticoid therapy. This case presents an uncommon combination of clinical features infrequently reported in the literature. Multi-organ IgG4-RD is a multisystemic mass, commonly creating diagnostic challenges for clinicians. Furthermore, and more importantly, it highlights the need to keep a differential of IgG4-RD in mind, to aid in the early and correct treatment of the disease.

Anti-mitochondrial antibodies detection assays for diagnosis of primary biliary cholangitis in southern Tunisia population / Techniques de détection des anticorps anti-mitochondries pour le diagnostic de cholangite biliaire primitive : étude dans une population sud-tunisienne

Anti-mitochondrial antibodies (AMA) represent serological markers of primary biliary cholangitis (PBC). Investigation of these autoantibodies can be performed by indirect immunofluorescence (IIF) on tissue sections or immunodot using M2 and M2-3E antigens. We aimed to evaluate the concordance of these immunological tests and their performance in PBC diagnosis. We reviewed sera which were tested for autoimmune liver disease anti-bodies by IIF (EUROIMMUN®) and immunodot (EUROIMMUN®). Results of IIF (AMA) and immunodot (anti-M2 and anti-M2-3E) were analyzed. A focus was given on positive results for AMA and/or anti-M2 and/or anti-M2-3E. According to available clinical data, patients were divided into two groups "PBC" and "Non PBC". Three-hundred-nineteen sera were tested by both techniques. Results of AMA, anti-M2 and anti-M2-3E were concordant in 296 cases (92.8%). Indeed, the three biomarkers were negative in 237 cases (74.3%) and positive in 59 cases (18.5%). Eighty-two sera were tested positive for AMA and/or anti-M2 and/or anti-M2-3E. Clinical data were available for 30 patients. In "PBC" group (n = 15), AMA, anti-M2 and anti-M2-3E antibodies were positive in 14/15 cases. PBC diagnosis was made in 12/15 patients without requiring liver biopsy. In "non PBC" group (n = 15), AMA, anti-M2 and antiM2-3E antibodies were positive in 9/15 cases. However, PBC diagnosis was not reached in the absence of other diagnostic criteria. IIF represents a first-line technique for AMA detection while immunodot is useful to confirm antigenic specificity in IIF-AMA positive cases. Anti-M2 and/or anti-M2-3E can be detected in some IIF-AMA negative cases. Interpretation of these tests'results relays mainly on clinical context.

Les anticorps anti-mitochondries (AAM) peuvent être recherchés par immunofluorescence indirecte (IFI) ou immunodot en utilisant les Ag M2 et M2-3E. Afin d'évaluer la concordance de ces tests et leur intérêt dans le diagnostic de cholangite biliaire primitive (CBP), nous avons comparé les résultats de recherche des AAM (IFI), anti-M2 et anti-M2-3E (immunodot) de 319 sérums. Selon les données cliniques disponibles, les patients avec au moins un marqueur positif ont été classés en deux groupes « CBP ¼ et « non CBP ¼. Les résultats des trois marqueurs étaient concordants dans 296 cas (92,8 %). Au moins un marqueur était positif dans 82 cas. Dans le groupe « CBP ¼ (n = 15), les trois marqueurs étaient positifs dans 14 cas. Dans 12 cas, le diagnostic était retenu sans recours à la biopsie hépatique. Dans le groupe « non CBP ¼ (n = 15), les trois marqueurs étaient positifs dans neuf cas, mais les autres critères de CBP n'étaient pas remplis. L'IFI demeure la technique de première intention pour la recherche des AAM ; l'immunodot permet de confirmer la spécificité antigénique. L'interprétation, notamment des cas discordants, repose surtout sur le contexte clinique.

Nonspecific interstitial pneumonia revealing an antisynthetase syndrome.

One of the most common interstitial lung diseases in antisynthetase syndrome is nonspecific interstitial pneumonia (NSIP). A 49-year-old woman presented with slow progression exertional dyspnea, myalgia, and arthralgia. The radiological findings indicated an NSIP pattern. Autoantibodies were found to be positive, but no lung biopsy was performed. Even though corticosteroid therapy significantly improved the patient's dyspnea, the patient developed mechanic's hands, the anti-synthetase antibody (PL12) became positive, and creatine phosphokinase (CPK) levels increased. As a result, the antisynthetase syndrome was established. The patient follow-up after three years revealed an improvement in symptoms under corticosteroid therapy.

Agranulocytosis in systemic lupus erythematosus: A case report.

Agranulocytosis is a rare acute condition characterized by severe a < gft (neutropenia in which the neutrophils count is less than 100/mm3. It can be classified into two categories, inherited, and acquired. Acquired agranulocytosis is not commonly caused by auto-immune diseases such as systemic lupus erythematosus (SLE). We report a case of a patient suffering from agranulocytosis related to SLE at disease onset, associated with other rare disease involvements.

About a rare association: Guillain-Barré Syndrome and polymyositis.

Guillain-Barré syndrome (GBS) and polymyositis (PM) are two rare autoimmune diseases, one of which affects the peripheral nervous system and other the muscle. We report the case of a young woman with no previous medical history who was hospitalized with an ascending paralysis associated with acute respiratory failure due to a GBS. The patient was treated with plasmapheresis with unfavorable outcome and permanent proximal muscular disability. The diagnosis of an associated PM was retained based on biological myolysis and the results of electromyography and muscular biopsy. To our knowledge, this association of GBS and PM has been reported only once in the literature. The search for syndromic associations in the presence of an autoimmune helps to avoid diagnostic errors.

Differential Expression of Anti-Inflammatory RNA Binding Proteins in Lupus Nephritis.

Lupus nephritis (LN) is a type of immunological complex glomerulonephritis characterized by chronic renal inflammation which is exacerbated by infiltrating leukocytes and fueled by a variety of pro-inflammatory cytokines. A profound understanding of the pathogenesis of LN is necessary to identify the optimal molecular targets. The role of RNA-binding proteins (RBPs) in post-transcriptional gene regulation in the immune system is being explored in greater depth to better understand how this regulation is implicated in inflammatory and autoimmune diseases. Tristetraprolin (TTP), Roquin-1/2, and Regnase-1 are 3 RBPs that play a critical role in the regulation of pro-inflammatory mediators by gating the degradation and/or translational silencing of target mRNAs. In this study, we proposed to focus on the differential expression of these RBPs in immune cells and renal biopsies from LN patients, as well as their regulatory impact on a specific target. Herein, we highlight a novel target of anti-inflammatory treatment by revealing the mechanisms underlying RBP expression and the interaction between RBPs and their target RNAs.

Cavitary lung opacity of unusual cause during Behçet disease.

Pulmonary artery aneurysm must be evoked in front of any hemoptysis in a patient with Behçet disease as it requires urgent immunosuppressive therapy and often surgery.

Th17 and Th1 cells in systemic lupus erythematosus with focus on lupus nephritis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by T cells imbalance. Indeed, a correlation between levels of Th17 cells and disease activity has been reported. Our work aimed to study the functional association of subpopulations of Th cells and SLE with (lupus nephritis, LN) or without (lupus erythematosus, LE) renal involvement in Tunisian patients through the detection of intracellular cytokines and surface marker expression. The IL23R and RORC mRNA expression levels were evaluated. The level of Th17 and Th1 cells was higher in LE and LN patients compared to healthy controls (HC) (p = 0.007 and p = 0.018, respectively), while Th1/17 cells were increased only in LN patients compared to HC (p = 0.011). However, no significant difference was described in the mRNA expression levels of RORC and IL-23R between SLE and HC. Our findings suggest that the Th1/Th17 differentiation mechanisms are altered in SLE and that this imbalance should have an important influence on the development and severity of the disease.

Selected plasma oxysterols as a potential multi-marker biosignature panel for Behçet's Disease.

Clinical, genetic, and medical evidence has shown the inflammatory vasculitis aspect of Behçet's Disease (BD). Whereas oxysterols are vital factors in inflammation and oxidative stress, it is still unknown whether they are involved in the pathophysiology of BD. The current study aims to explore the profile of oxysterols in plasma of BD patients. Thirty patients diagnosed with BD and forty healthy controls matched for age and gender were included. Results showed that the cholestane-3ß,5α,6ß-triol, 27-hydroxycholesterol (27-OHC) and cholestanol levels were higher in BD than controls. In addition, plasma levels of 7-ketocholesterol (7-KC) and 25-hydroxycholesterol (25-OHC) were lower in BD patient. However, levels of 24S-hydroxycholesterol (24-OHC) did not significantly differ. For BD patients, the plasma 7-KC level was negatively correlated with the BD activity index (BDAI) while 27-OHC was positively correlated with high-sensitivity C-reactive protein (hs-CRP) in patients with active course of the disease. According to ROC analysis, a remarkable increase in the area under the curve (AUC) with a higher sensitivity (Se) and specificity (Sp) for 7-KC, 25-OHC and 27-OHC combined markers was observed. The present study indicated that the identification of the predictive value of these three-selected biomarkers related to oxidative stress and inflammation in patients should lead to a better identification of the etiological mechanism of BD.

Coexistence of thrombotic thrombocytopenic purpura and adult-onset Still's disease.

The association of Thrombotic thrombocytopenic purpura (TTP) and adult-onset Still's disease (AOSD) is very uncommon. Hereby, we present a case of TTP occurring in patient with a known AOSD and the successful outcome after plasma exchanges.

Role of innate immune receptors TLR4 and TLR2 polymorphisms in systemic lupus erythematosus susceptibility.

AIM: Through their recognition of various bacterial cell wall components, TLR2 and TLR4 participate in the innate response and modulate the activation of adaptive immunity. Therefore, the genetic background of these receptors might play a crucial role in autoimmune diseases such as systemic lupus erythematosus (SLE). In this study, we investigated the possible association between polymorphisms within TLR2 and TLR4 genes with SLE susceptibility. MATERIAL AND METHODS: A total of 100 SLE patients and 200 unrelated healthy controls of the Tunisian population were enrolled in the study.TLR4rs4986790, TLR4rs4986791, and TLR2rs5743708 genotyping were performed using a polymerase chain reaction-restriction fragment length polymorphism method. The number of guanine-thymine (GT) repeat microsatellite in the intron 2 of TLR2 gene was analyzed by sequencing. RESULTS: We reported a lack of allelic and genotypic association between SNPs of TLR4 and TLR2 genes and SLE pathogenesis. No correlation was found with any SLE features. However, SLE susceptibility was associated with the GT repeat microsatellite polymorphism in the human TLR2 gene. Further subclassification of alleles into three subclasses revealed a significant association between the long-sized repeats ((GT) >23) and SLE. CONCLUSION: Though the results showed the absence of genetic association of TLR4 and TLR2 SNPs with the risk of developing SLE, we have identified a protective association between the microsatellite polymorphism in intron 2 of the TLR2 gene and SLE. Functionally, these (GT)n repeats may confer modifying effects or susceptibility to certain inflammatory conditions.

Annexin A1 and its receptor gene polymorphisms in systemic lupus erythematosus in the Tunisian population.

BACKGROUND: An association between ANXA1, FPR1 and FPR2 gene polymorphisms and the patho-physiology of many human diseases was suggested by numerous studies. OBJECTIVE: Our study aimed to evaluate association between common polymorphisms in the 9q21.13 and 19q13.41 and susceptibility to systemic lupus erythematosus (SLE) in the Tunisian population. MATERIALS: We performed a case-control study on 107 Tunisian SLE patients and 122 healthy controls to explore 9 polymorphisms of the three studied genes: rs2811226 and rs3739959 (ANXA1), rs5030880, rs1042229, rs1461765570, rs17849971, rs867228 (FPR1), rs17694990 and rs11666254 (FPR2). RESULTS: Four polymorphisms were found to be linked with SLE susceptibility: rs3739959-ANXA1 > G and GG (p = 0.021, OR = 1.73 and p = 0.014, OR = 2.06 respectively), rs867228-FPR1 > TT (p = 0.014, OR = 4.59), rs11666254-FPR2 > GG (p = 0.019, OR = 8.34) and rs17694990-FPR2 > T (p = 0.05, OR = 1.506). In homogenous groups of SLE patients depending on clinical manifestations and serological results, previous associations were confirmed with a panoply of manifestations of lupus including lupus nephritis, malar rash, mouth ulceration and hypocomplementia. CONCLUSION: Our study showed an association between ANXA1 > rs3739959, FPR1 > rs867228, FPR2 > rs11666254, FPR2 > rs17694990 and SLE susceptibility. Our results also showed a strong association between the two ANXA1 studied SNPs and LN which allowed us to suggest these two SNPs as biomarkers of LN development in SLE. Further research is needed to understand by which mechanism the gene variants affect susceptibility to SLE. Key Points • Lupus erythematosus is an autoimmune disease in which a panoply of factors are implicated • Annexin A1 interaction with its receptors are suggested as a target in therapy of a panoply of human disease in particular cancers • The present results highlighted the implication of Annexin A1 and its receptors gene polymorphisms in the physiopathology of lupus, in particular in the involvement of renal and cutaneous lesions.

[Diffuse infiltrating lung disease secondary to antisynthetase syndrome: a case report]. / Pneumopathie infiltrante diffuse secondaire à un syndrome des antisynthétases: à propos d´un cas.

Diffuse infiltrate lung diseases (DILDs) are frequent in patients with connective tissue diseases. They can be suggestive of connective tissue diseases or occur during follow-up. Antisynthetase syndrome (ASS) is a complex and heterogeneous connective tissue disease. Antisynthetase antibodies, in particular the anti-Jo1 antibody, are found in patients with this syndrome. The prognosis of ASS is conditioned by the occurrence of DILD and its severity, thus guiding therapeutic management. We here report the case of a 57-year-old female patient presenting with acute febrile DILD revealing ASS. Outcome was favorable under bolus corticosteroids in combination with cyclophosphamide treatment.

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.