Atypical Familial Mediterranean Fever Presenting with Recurrent Upper Back Pain: A Case Report.

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease that is characterized by recurrent episodes of fever, serositis, and synovitis. FMF synovitis attacks resemble the clinical presentation of acute monoarthritis with pain and hydrarthrosis, which always resolve spontaneously. In most cases, colchicine will prevent these painful arthritis attacks in FMF. However, distinguishing these arthritis episodes from other febrile attacks with various clinical manifestations, including serositis, is important. We describe a Japanese patient with FMF who presented a febrile attack with severe abdominal and upper back pain (peri-scapula lesion), without any other joint involvement. A 44-year-old female patient presented with recurrent episodes of fever with abdominal and back pain. She carried heterozygous variants in exon 3 of the MEFV gene (P369S/R408Q). She was diagnosed with FMF according to Tel-Hashomer's diagnostic criteria for FMF. Colchicine treatment improved her febrile attcks with peritonitis, however, severe back pain was sustained. This unique aspect of severe pain attack was successfully resolved by canakinumab treatment, which is a specific interleukin-1ß monoclonal antibody, and was finally diagnosed as FMF-related shoulder joint synovitis. Further investigations were needed to evaluate the effectiveness of interleukin-1 antagonists against colchicine-resistant arthritis in FMF patients.

Checkpoint-inhibitor induced Polyserositis with Edema.

BACKGROUND: As immune checkpoint inhibitors (ICI) are increasingly being used due to effectiveness in various tumor entities, rare side effects occur more frequently. Pericardial effusion has been reported in patients with advanced non-small cell lung cancer (NSCLC) after or under treatment with immune checkpoint inhibitors. However, knowledge about serositis and edemas induced by checkpoint inhibitors in other tumor entities is scarce. METHODS AND RESULTS: Four cases with sudden onset of checkpoint inhibitor induced serositis (irSerositis) are presented including one patient with metastatic cervical cancer, two with metastatic melanoma and one with non-small cell lung cancer (NSCLC). In all cases treatment with steroids was successful in the beginning, but did not lead to complete recovery of the patients. All patients required multiple punctures. Three of the patients presented with additional peripheral edema; in one patient only the lower extremities were affected, whereas the entire body, even face and eyelids were involved in the other patients. In all patients serositis was accompanied by other immune-related adverse events (irAEs). CONCLUSION: ICI-induced serositis and effusions are complex to diagnose and treat and might be underdiagnosed. For differentiation from malignant serositis pathology of the punctured fluid can be helpful (lymphocytes vs. malignant cells). Identifying irSerositis as early as possible is essential since steroids can improve symptoms.

Refractory serositis in Gorham-Stout syndrome.

BACKGROUND: Gorham-Stout syndrome (GSS) is a rare disorder with various presentations and unpredictable prognoses. Previous understandings of GSS mainly focused on progressive bone destruction, while we identified a group of GSS patients with serous effusion as the first symptom. This study aimed to investigate the clinical characteristics of patients with GSS having serous effusion as the first symptom. METHODS: Patients diagnosed with GSS were identified through the Peking Union Medical College Hospital Medical Record System. The demographic, clinical, laboratory, and imaging data were collected. Patients who first presented with serous effusion were recruited into the serous group, while those with bone destruction were recruited into the bone group. RESULTS: Of the 23 patients with GSS enrolled, 13 were in the bone group and 10 in the serous group. The median disease duration was shorter and exercise tolerance was lower in the serous group. Despite less frequent bone pain in the serous group, the frequency of bone involvement was similar to that in the bone group. Patients in the serous group had higher rates of bilateral pleural effusion and multiple serous effusion. However, serous effusion also developed with disease progression in the bone group. Of the 17 patients treated with bisphosphonates, 14 reached bone-stable state. However, 5 out of 10 patients with serous effusion still had refractory effusions after bisphosphonates treatment. Three patients received sirolimus treatment, with an improvement in serous effusion. Seventeen patients were followed up; three patients died, two in the bone group and one in the serous group. CONCLUSIONS: This study discovered that GSS could first be presented with serous effusion. We believe that this may be a new phenotype of the disease. Sirolimus might help in controlling serous effusion and improving prognosis.

Chronic Myelomonocytic Leukemia Presenting With Polyserositis and Seropositivity for Rheumatoid Arthritis.

Chronic myelomonocytic leukemia (CMML) is a rare clonal stem cell disorder associated with clinical and pathologic of myelodysplasia and myeloproliferation. Systemic autoimmune/inflammatory disorders (SAID) and polyserositis have been associated with CMML. These manifestations can be observed concomitantly, shortly before diagnosis or anytime along the course of illness. We report a case of myeloproliferative CMML who presented with polyserositis and positive serology for rheumatoid arthritis. Retrospective studies of myelodysplasia/CMML have reported 15% to 25% incidence of SAID. The most commonly observed disorders include systemic vasculitis, connective tissue diseases, polychondritis, seronegative arthritis, and immune thrombocytopenia. SAID does not confer adverse prognosis in retrospective studies. Polyserositis is less common; this may result from leukemic infiltrate or result from autoimmunity. Treatment of serositis includes steroids and cytoreductive agents. Serositis may confer poor prognosis and hypomethylating therapy may improve the outcome.

Therapeutic management of idiopathic recurrent serositis: a retrospective study.

OBJECTIVE: Idiopathic recurrent serositis (IRS) is the most frequent serositis encountered in real-life medical sceneries, and its management represents a therapeutic challenge. There are few epidemiologic data related to IRS, though most studies have focused on recurrent pericarditis, revealing that 70% of all forms of pericarditis are idiopathic and caused by innate immunity abnormalities. The aim of this study was to evaluate outcome and recurrence rates of patients with IRS, assessing management modalities used in our Periodic Fever Centre of the Gemelli Hospital, Rome, Italy, in comparison with previous treatments in other centres. PATIENTS AND METHODS: Retrospectively, we analyzed the medical charts of 57 unselected patients with history of IRS managed during the period 1998-2017. RESULTS: A strong heterogeneity emerged by evaluating treatments of this cohort. In particular, in our Centre there was a larger use of combined therapies: 14 patients out of 27 (52%) were treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and colchicine, compared to only 2 patients (7.4%) previously treated with combined treatments. We used corticosteroid monotherapy only in 1 case, against 7 from other centres. The mean duration of NSAID treatment in other hospitals was 43.8 days (SD ±27.40) and 191.25 days (SD ±42.23) in our Centre; the mean duration of corticosteroid treatment in other hospitals was 101.5 days (SD ±56.40) and 180.7 days (SD ±84.87) in our Centre. Colchicine was administered in other hospitals for the same duration of NSAIDs, and corticosteroids with an average duration of 111 days (SD ±30); conversely, we administered colchicine for an average duration of 250.12 days (SD ±80.7). Relapses of IRS were reported in 1/3 of cases who had discontinued therapies. CONCLUSIONS: The overall duration of treatments to manage IRS has a weight in terms of patients' outcome. A reduced duration of therapy with corticosteroids and a longer duration of therapy with NSAIDs determine a longer disease-free interval. A significant discriminating effect in terms of risk of IRS recurrence relies in an earlier combination therapy with colchicine independently from the start with either NSAIDs or corticosteroids. Finally, the evaluation of genes causing autoinflammatory diseases has not revealed any pathogenetic variants in a subcohort of 20/57 patients with IRS.

A rare combination: chylous polyserositis and autoimmune myelofibrosis as a presentation of systemic lupus erythematosus.

Chylous polyserositis and autoimmune myelofibrosis occurring concomitantly inn a case of SLE are a rare phenomenon. We here report a case of a 38-year-old woman who was admitted with a history of cough and shortness of breath for 1½ months along with fever and abdominal distension for 1 month. She also had arthralgias, weight loss and pancytopenia. She was diagnosed as a case of SLE with Chylous polyserositis and autoimmune myelofibrosis. She was started on steroids and immunosuppressive therapy, to which she responded. To summarize, this is the first case report where chylous polyserositis and pancytopenia due to autoimmune myelofibrosis occurred which was responsive to steroids and immunosuppressive therapy.

A case of drug-induced lupus erythematosus secondary to trimethoprim/sulfamethoxazole presenting with pleural effusions and pericardial tamponade.

We report a case of drug-induced lupus erythematosus (DILE) secondary to trimethoprim/sulfamethoxazole (TMP/SMX) in a patient with underlying inflammatory bowel disease (IBD). The initial presentation was with febrile pleural and pericardial effusions followed by cardiac tamponade. The patient was treated with a short course of corticosteroids with complete resolution of symptoms. To our knowledge this is the first reported case of TMP/SMX-induced DILE presenting with life-threatening serositis. When confronted with sterile exudative effusions, clinicians should strongly consider non-infectious etiologies.

Antibacterial, anti-inflammatory, and antioxidant effects of Yinzhihuang injection.

The Yinzhihuang injection, a traditional Chinese medicine, has been the recent target of increasing interest due to its anti-inflammatory properties. The molecular basis by which Yinzhihuang injection could cure Riemerella anatipestifer (RA) serositis in ducks is unclear. This study evaluated the antibacterial, anti-inflammatory and antioxidant effects of Yinzhihuang injection, using disease models of RA-induced infectious serositis in ducks and heptane-induced inflammation in mice and rats. The duck mortality rate was reduced from 60% to 20% and both the inflammatory response and histological damage were ameliorated by treatment with Yinzhihuang injection (0.02 g/kg). Further studies indicated that superoxide dismutase (SOD), nitric oxide synthase (NOS), and inducible nitric oxide synthase (iNOS) were elevated while malondialdehyde (MDA), nitric oxide (NO) and RA growth were inhibited when the ducks were treated by Yinzhihuang injection. In addition, Yinzhihuang injection (0.04 g/ml) effectively inhibited xylene-induced auricle swelling in mice, (demonstrating an inhibition rate of 35.21%), egg albumen-induced paw metatarsus swelling in rats, (demonstrating an inhibition rate of 22.30%), and agar-induced formation of granulation tissue. These results suggest that Yinzhihuang injection ameliorates RA-induced infectious serositis in ducks by modulation of inflammatory mediators and antioxidation.

Usefulness of tumor marker CA-125 serum levels for the follow-up of therapeutic responses in tuberculosis patients with and without serositis.

The aim of this study was to determine the usefulness of cancer antigen 125 (CA-125) serum levels in patients with tuberculosis (TB) with and without tuberculous serositis. A total of 64 TB patients with a mean age of 58.17 ± 19.05 years were enrolled in this observational case series study. All patients underwent blood sampling for the measurement of CA-125 serum levels before treatment. If the CA-125 serum levels were found to be elevated, the patients underwent blood sampling in the initial treatment phase, continuation treatment phase, and every 6 months thereafter for 2 years. The treatment outcomes of the pulmonary TB group were evaluated using chest radiography and sputum examinations, and those of the tuberculous serositis group were evaluated on the basis of the amounts of fluid determined by ultrasound. All patients in the tuberculous serositis group and 45% of the patients in the pulmonary TB group had elevated CA-125 serum levels before treatment. The pretreatment mean CA-125 serum level was significantly higher in the tuberculous serositis group than in the pulmonary TB group. CA-125 serum levels decreased along with improvement in anti-TB treatment outcomes in both the groups. In conclusion, the CA-125 serum levels in combination with clinical responses, chest radiography, and sputum examinations, can offer better monitoring of therapeutic responses in anti-TB treatment.

Familial Mediterranean fever presenting with pulmonary embolism.

Familial Mediterranean fever (FMF) is the autoinflammatory disease and hereditary periodic fever syndrome that most commonly affects people of Eastern Mediterranean origin. It is characterized by recurrent self-limited attacks of fever and serositis, with an increase in acute-phase reactant markers, and is transmitted in an autosomal recessive pattern. Inflammation shifts the hemostatic mechanisms favoring thrombosis. There are few reports of an increased risk of hypercoagulability in patients with FMF in the absence of amyloidosis and nephrotic syndrome. In this case report, we describe a 43-year-old Turkish patient who presented with right-sided pleuritic chest pain and pulmonary embolism. The patient described having prior similar attacks of serositis, but had never been diagnosed with FMF. Further workup revealed an increase in acute phase reactants, negative hypercoagulability studies and heterozygosity for the M694V mutation in the pyrin (MEFV) gene. We identified untreated FMF and chronic inflammation as his only risk factor for pulmonary embolism. With this case report, we support recent studies that have demonstrated that inflammation may lead to prothrombotic states in patients with FMF.

[Severe disseminated constrictive polyserositis in a patient with rheumatoid arthritis].

Constrictive polyserositis (pleuritis, pericarditis) is a syndrome within the underlying disease (tuberculosis, periodic disease, rheumatoid arthritis, systemic lupus erythematosus, asbestos, silicosis, uremia, some genetic diseases), a complication due to chest surgery or radiation or drug therapy, is occasionally idiopathic (fibrosing mediastinitis). There are frequently great difficulties in making its nosological diagnosis. The paper describes a patient in whom the onset of disease was exudative pleurisy with the signs of constriction, arthralgias; pleural punctures provided serous exudates with 80% lymphocytes. A year later there was ascitis and shin and foot edemas, which concurrent with hepatomegaly and cholestasis was regarded as cryptogenic liver cirrhosis. The signs of constrictive pericarditis were further revealed. The disease was complicated by the development of pulmonary artery thromboembolism (PATE) (which required the use of warfarin) and hemorrhagic vasculitis. Therapy with metipred in combination with isoniazid yielded a slight effect. The diagnoses of tuberculosis, liver cirrhosis, and autoimmune hepatitis, systemic vasculitis were consecutively rejected; the diagnosis of rheumatoid polyarthritis with systemic manifestations was made, by taking into account persistent arthalgias with the minimum signs of arthritis, noticeably increased C-reactive protein, rheumatoid factor, and cyclic citrullinated peptide antibodies (CCPA); plasmapheresis, therapy with metipred and methotrexate, and subtotal pericardectomy were performed. Constrictive polyserositis concurrent with PATE, hemorrhagic vasculitis (probably, drug-induced one), and hepatic lesion has been first described in a CCPA-positive patient with rheumatoid arthritis in the presence of moderate true arthritis (during steroid therapy).

Severe anemia, panserositis, and cryptogenic hepatitis in an HIV patient infected with Bartonella henselae.

Bartonella spp. constitute emerging pathogens of worldwide distribution. Bacillary angiomatosis is the most frequent skin manifestation of bartonelloses; nevertheless, B. henselae infection should always be considered systemic, especially in immunodeficient individuals. The authors report the case of an AIDS patient with bacillary angiomatosis, who had concurrent severe anemia, hepatitis, peritonitis, pleuritis, and pericarditis. Clinical manifestation, electronic microscopic examination of erythrocytes, and histopathology of a papule biopsy suggested a Bartonella sp. infection. Multiple genes were target by PCR and B. henselae DNA was amplified and sequenced (GenBank accession number EF196804) from the angiomatous papule. Treatment with clarithromycin resulted in resolution of the bacillary angiomatosis, fever, anemia, panserosites, and hepatitis.

[Rituximab for treatment of patients with systemic autoimmune diseases]. / Utilidad del rituximab en el tratamiento de pacientes con enfermedades sistémicas autoinmunitarias.

BACKGROUND AND OBJECTIVE: To assess the value of rituximab in systemic autoimmune diseases which are refractory to others treatments. PATIENTS AND METHOD: Prospective study on 12 patients -7 with systemic lupus erythematosus (SLE), 4 with Wegener's granulomatosis (WG), and 1 with overlapping connective disease and autoimmune thrombocytopenia-, controlled in a specialized unit of a tertiary hospital. Four weekly doses of rituximab, 2 biweekly doses of cyclophosphamide, and glucocorticoids were administered to all patients, and other immunosuppressants were also administered as considered necessary in each case. RESULTS: Mean follow up after treatment with rituximab was 12.8 moths for SLE patients and 12.3 for WG patients. In SLE patients, proteinuria was reduced below 1 g daily in 5 cases (83%), with a clear parallel improvement in the urinary sediment. Serositis was resolved in both cases. One patient required 3 treatment cycles to obtain an adequate response and another required a second cycle for relapse. Only one patient with WG had a favorable response. The patient treated for autoimmune thrombocytopenia had a favorable response, with no relapses, and creatine-kinase levels also tended to return to normal. There were 2 serious adverse events (terminal renal failure and serious colitis in a patient with SLE, and death of one patient with WG), that were not adjudicated directly to rituximab. Immunoglobulin levels did not change substantially. There were no infusion reactions or associated infections. CONCLUSIONS: Rituximab was useful in patients with SLE refractory to other immunosuppressants. On the contrary, its efficacy in WG was limited. The response of thrombocytopenia was complete and maintained.