Development of sulfasalazine-associated drug-induced lupus erythematosus in patient with rheumatoid arthritis (clinical case)

Drug-induced lupus syndrome (DLS) is a rare adverse event with a variety of drugs. More than a hundred of drugs are known that can cause the development of DLS, and this list is growing as new drugs appear. Physicians of any specialty can face such complications of therapy and should be aware of this pathology. The article presents an analysis of a clinical case of DLS development against the background of long-term administration of sulfasalazine in a patient with a reliable diagnosis of rheumatoid arthritis, as well as a literature review, which includes data on the prevalence, drug groups, clinical manifestations, diagnosis and treatment of this pathology.

Low prevalence of anti-SSA (anti-Ro) and anti-SSB (anti-La) autoantibodies in female patients with rheumatoid arthritis with a wish to conceive

ObjectivesGuidelines advise to test for anti–Sjögren's-syndrome-related antigen A (anti-SSA) and anti–Sjögren's-syndrome-related antigen B (anti-SSB) antibodies in all patients with rheumatoid arthritis (RA) who wish to conceive. Our objective was to determine the prevalence and titres of anti-SSA and anti-SSB autoantibodies in patients with RA with a wish to conceive or pregnant.MethodsPatients were derived from two large cohorts on RA and pregnancy (PARA cohort and PreCARA cohort). In addition, to determine the clinical relevance of searching for anti-SSA and anti-SSB in patients with RA, we studied the prevalence of the maternal diagnosis of RA in the French national registry of neonatal lupus syndrome (NLS) and congenital heart block (CHB).Results26 out of 647 patients with RA had detectable anti-SSA and/or anti-SSB. Anti-SSA was detected in 25 out of 647 patients (3.9%) (Ro-52, n=17; Ro-60, n=19), anti-SSB in 7 out of 647 (1.1%). Thirteen women had a titre of >240 units/mL of anti-SSA antibodies. The prevalence of anti-SSA and/or anti-SSB was higher in rheumatoid factor (RF)-positive patients compared with RF-negative patients (5.1% vs 1.6%, p=0.04). No cases of CHB and/or NLS in the offspring were observed. In the French national register, the prevalence of RA in mothers with SSA related CHB was 1.5%.ConclusionAnti-SSA and anti-SSB have a low prevalence in patients with RA who wish to conceive. Especially for RF-negative patients, the current advise to test for anti-SSA and anti-SSB should be reconsidered.

Diffuse alveolar hemorrhage associated with ustekinumab treatment

Purpose A case of diffuse alveolar hemorrhage (DAH) occurring as a reaction to ustekinumab therapy is reported. Summary After starting ustekinumab for treatment of psoriatric arthritis, a 46-year-old female presented with flu-like symptoms and cough with blood-tinged sputum that had begun 1 week previously. Her initial computed tomography scan of the chest demonstrated bilateral ground-glass opacities. On bronchoscopy, the bronchoalveolar lavage (BAL) return became bloodier from sample 1 to samples 2 and 3. Her BAL fluid was more than 90% hemosiderin-laden macrophages, a finding consistent with DAH. We ruled out infectious etiologies and other common vasculitis conditions that can cause DAH. A diagnosis of ustekinumab-induced DAH was made due to a temporal relationship between initiation of the drug and the patient’s presentation and the absence of infection and other alternate diagnosis. Prior case reports including ustekinumab-induced pneumonitis, interstitial lung disease with a granulomatous component, and lupus syndrome have been reported, with this being the first case of DAH in a patient undergoing treatment of psoriatic arthritis. Conclusion A 46-year-old woman developed DAH during ustekinumab treatment. Symptoms abated after drug discontinuation and supportive treament. Clinicians must remain mindful of this rare complication of ustekinumab use in order to avoid potential delays in appropriate DAH treatment.

Sex-specific differences in the function and differentiation of ABCs mark TLR7-driven immunopathogenesis

ABSTRACTSex differences characterize immune responses to viruses like SARS-CoV2 and autoimmune diseases like SLE. ABCs are an emerging population of CD11c+ T-bet+ B cells critical for antiviral responses and autoimmune disorders. DEF6 and SWAP70, are two homologous molecules whose combined absence in double-knock-out mice (DKOs) leads to a lupus syndrome in females marked by an accumulation of ABCs. Here we demonstrate that DKO ABCs exhibit sex-specific differences in their expansion, upregulation of an ISG signature, and further differentiation. BCR sequencing and fate mapping experiments reveal that DKO ABCs undergo oligoclonal expansion and differentiate into both CD11c+ and CD11c− effector populations with pathogenic and proinflammatory potential. Tlr7 duplication in DKO males overrides the sex-bias and further augments the dissemination and pathogenicity of ABCs resulting in severe pulmonary inflammation and early mortality. Thus, sexual dimorphism shapes the expansion, function, and differentiation of ABCs contributing to the sex-bias that accompanies TLR7-driven immunopathogenesis.

Complete heart block in a 40-year-old man with anti-SSA/Ro autoantibodies

Atrio-ventricular dissociation (AVD), including complete heart block (CHB), are far more common in the elderly. We report a rare case of CHB in a 40-year-old man, who tested positive for anti-Ro autoantibodies without systemic features. He had been suffering for giddiness over the previous two months. On arrival, his electrocardiogram revealed high-degree AVD. Upon further history, he mentioned that his 68-year-old mother with systemic lupus erythematosus (SLE) had suffered from similar episodes, requiring a permanent pacemaker implantation. On further investigation, he tested positive for antinuclear antibodies (ANA), anti-SSA/Ro and anti-RNP antibodies. However, from history and clinical examination, he had not manifested any articular, extra-articular or extra-glandular features suspicious of rheumatological conditions. Following a failed trial of intravenous hydrocortisone, he subsequently had a permanent pacemaker implanted himself. Although difficult to ascertain whether our patient suffered from a congenital form of anti-SSA/Ro-related CHB, there is evidence to suggest delayed presentation of CHB in those with anti-SSA/Ro and neonatal lupus syndrome. Anti-SSA/Ro antibodies without systemic features can be present in 3% of the population, although this occurs more commonly in the presence of a confirm diagnosis of SLE, Sjögren’s syndrome or poly- and dermatomyositis. Despite the scarcity of evidence, a trial of steroid-based treatment was attempted prior to subjecting the young patient to a permanent pacemaker and its associated complications. To our knowledge, this is only the second case of isolated anti-SSA/Ro syndrome presenting with CHB reported in the literature.

Pulmonary hypertension associated with congenital heart block and neonatal lupus syndrome: A series of four cases

Objective Neonatal lupus syndrome has multisystemic manifestations among which pulmonary involvement has been rarely reported. We describe the clinical presentation, management, and outcome of a series of four neonates who developed reversible pulmonary hypertension associated with auto-immune congenital complete heart block. Method Data from the French registry of neonatal lupus syndrome were retrospectively reviewed. Results Between 2000 and March 2020, 231 children were included in the French registry, four/73 followed in our institution developed pulmonary hypertension. Diagnosis was suspected on transthoracic echocardiography at a median age of 42 days [range 10-58], and confirmed by right heart catheterization in all; 2 of them where paced at time of diagnosis and 2 were not. All had some degree of hypoxemia and respiratory distress. Hypoxemia was always reversible under O2 et NO. Lung CT demonstrated ground glass anomalies in all. One patient had a lung biopsy consistent with pulmonary hypertension secondary to lung disease. Management included immunosuppressive therapy in 3 associated with sildenafil in 2. Pulmonary hypertension resolved in all at a median age of 4 weeks [range 3-6] after treatment initiation and after one year for the one child who did not receive specific treatment. Conclusion Clinical, hemodynamical, imaging and histological findings advocate for pulmonary hypertension associated with respiratory disease as a rare manifestation of neonatal lupus syndrome.