Successful long-term systemic sclerosis treatment by high-frequent low-dose B cell-depleting therapy.

OBJECTIVES: Systemic sclerosis (SSc) is a multiorgan disease with a 10-year mortality rate of up to 50 %. B cell-depleting therapy with rituximab (RTX) appears effective in SSc treatment, but data from randomized controlled trials (RCTs) are lacking, and the frequency and dosage of RTX in SSc have no consensus. We aimed to evaluate the long-term efficacy and safety of quarterly RTX administration in SSc. METHODS: This study retrospectively analyzed 40 patients with SSC treated with RTX twice within 14 days every 3 months from 2010 to 2020. The patients fulfilled the LeRoy and the American College of Rheumatology/European League Against Rheumatism Criteria for SSc. Modified Rodnan skin score (mRSS), lung function test results, and serum immunoglobulin (IgG, IgA, and IgM) concentrations were analyzed. RESULTS: A total of 40 patients with SSc received RTX over a median time of 3.9 years (range: 1-10 years). The median mRSS (baseline: 19, 24 months: 16, p < 0.001) demonstrated a significant improvement, and the predicted forced vital capacity was stable. No new or unexpected safety signals, especially regarding treatment-related infectious adverse events, were observed. Immunoglobulin concentrations were within normal range, and specific antibodies to pneumococcal polysaccharides were preserved despite long-term B cell-depleting therapy. None of the patients died during the observation period of up to 10 years. CONCLUSION: SSc was effectively and safely treated with low-dose RTX quarterly. RCTs are warranted to validate the advantage of continuous B cell depletion by quarterly low-dose RTX administration compared to other treatment intervals.

[IL-1-blockade with Anakinra during pregnancy : Retrospective analysis of efficacy and safety in female patients with familial Mediterranean fever]. / IL-1-Blockade mit Anakinra in der Schwangerschaft : Retrospektive Wirksamkeits- und Sicherheitsanalyse bei Patientinnen mit familiärem Mittelmeerfieber.

OBJECTIVE: To retrospectively assess and analyze the clinical efficacy and safety of off-label interleukin-1 (IL-1) blockade with anakinra during pregnancy of patients with familial Mediterranean fever (FMF). METHODS: Retrospective analysis of clinical and laboratory parameters making use of an electronic database system. Detailed descriptions of the genotype and phenotype of FMF are given and the course of the pregnancy and fetal development are reported. RESULTS: The data of three patients and a total of four pregnancies under treatedment with anakinra were analyzed. All patients were of Mediterranean origin, fulfilled the Tel Hashomer criteria for diagnosis of FMF and had a confirmed mutation in the MEFV gene. In all patients, treatment with anakinra was initiated due to an insufficient treatment response to colchicine. Anakinra led to a rapid response in all patients. In three pregnancies anakinra treatment was continued during the whole pregnancy, while in one pregnancy anakinra was started in the second trimester because of uncontrolled FMF activity. Fetal development was normal in all pregnancies. In two patients the fetuses were carried to term, while in one patient a primary cesarean section was carried out in week 33 because of an increased risk for complications. All children showed an unremarkable early childhood development without any signs of an existing disease. CONCLUSION: The data of our retrospective analysis suggest that IL-1-blockade by anakinra is an effective and safe treatment in pregnant women suffering from FMF, which can reliably prevent disease flares. In the four pregnancies presented the use of anakinra did not result in impaired fetal and (early) childhood development.

[Off-label biologic therapy of ANCA-associated and non-ANCA-associated small-vessel vasculitis : Efficacy and safety analysis of a national registry (GRAID2)]. / Off-label-Biologikatherapie von ANCA-assoziierten und nicht-ANCA-assoziierten Kleingefäßvaskulitiden : Wirksamkeits- und Sicherheitsanalyse eines nationalen Registers (GRAID2).

OBJECTIVE: To evaluate the clinical efficacy and safety of off-label biological therapies in patients with ANCA-associated vasculitis (AAV) and non-ANCA-associated small-vessel vasculitis (nAAV) in clinical practice. METHODS: The German Registry in Autoimmune Diseases 2 (GRAID2) is a national, retrospective, non-interventional, multicentre observational study (August 2006 until December 2013) on patients with autoimmune diseases refractory to standard immunosuppressive therapy treated with off-label biologicals. RESULTS: Data from 64 patients (20.6% of all GRAID2 patients) were collected: 54 patients (84.4%) had ANCA-associated vasculitis (AAV) and 10 patients (15.6%) had non-ANCA-associated small-vessel vasculitis (nAAV). Of the AAV patients, 96.3% were treated off-label with rituximab (RTX) and 3.7% with tumor necrosis factor alpha (TNFα)-inhibitors. Of patients with nAAV, 30% were treated with RTX, 60% with TNFα-inhibitors, and 10% with tocilizumab. The main reasons for off-label biological treatment in AAV patients were pulmonary, renal, or ear, nose, and throat involvement. These manifestations clearly improved in most patients after off-label biological therapy was initiated. Daily glucocorticoid dosage could be reduced. The off-label biological therapy was generally well tolerated. In AAV patients, 4.18 severe infections per 100 patient years were observed. There was one death in the nAAV group caused by fungal infection and ileus. A correlation between this fatality and RTX treatment was regarded as possible. CONCLUSION: Safety and efficacy of off-label RTX-treatment in AAV-patients could be assessed in the GRAID2 data. Results point to good efficacy and safety of RTX in this special patient cohort and support the approval of RTX for AAV induction therapy.

[Factitious disorder--fever and delayed wound healing]. / Artifizielle Krankheit--Fieber und verzögerte Wundheilung.

HISTORY AND ADMISSION FINDINGS: A 23-year-old woman was admitted to the department of rheumatology for detailed diagnostic tests for a suspected immune deficiency. Over the past 3 years, she has had repeated unexplained febrile episodes and impaired wound healing, which required permanent antibiotic treatment. INVESTIGATIONS AND DIAGNOSIS: Extensive tests initially showed no definitively diagnostic findings. Based on various clinical and inconsistencies in biochemic tests, the suspicion of a self-inflicted cause increased. In several interviews with a psychologist of the psychosomatic consultation service, the patient finally admitted manipulation by means of i. v. application of bacterially contaminated water. THERAPY AND CLINICAL COURSE: The self-inflicted injuries were interpreted as the consequence of a serious psychological trauma, as well as a self-healing attempt to prevent an emotional breakdown. The trust which the patient developed in her specialist carers after admitting the deception, made it possible to motivate her to continue psychotherapy. CONCLUSION: If a factitious disorder is suspected, the doctor should not be too precipitous in confronting the patient without expression of empathy, but rather respect the self-inflicted injury as a measure of self-preservation. Such non-confrontational behavior on the part of the carer enables the patient to accept the offer of psychotherapy without losing face.

3-T MRI reveals cranial and thoracic inflammatory changes in giant cell arteritis.

Giant cell arteritis (GCA) is a diagnostic challenge. The correct diagnosis is needed for immediate initiation of corticosteroid treatment since blindness is a dreaded complication. Typically, the superficial cranial arteries are affected by this granulomatous vasculitis of large- and medium-sized arteries. However, GCA is not limited to the cranial arteries. Involvement of various arteries such as the cervical and thoracic arteries can also occur. Here, we report a case of histologically proven GCA with cranial and extracranial involvement. We illustrate the usefulness of a comprehensive vascular high-resolution magnetic resonance imaging examination that combines assessment of mural inflammatory changes of the small temporal and occipital arteries with the evaluation of extracranial vasculature to assist in the difficult non-invasive diagnosis and to determine the extent of this inflammatory disease.