Familial cold autoinflammatory syndrome with rheumatoid arthritis.

Familial cold autoinflammatory syndrome (FCAS) is a cryopyrin-associated periodic syndrome that presents with episodic fever, skin rash, and joint pain after exposure to cold temperatures. Although the diagnosis is often singular, there are several instances of concurrent underlying autoimmune pathologies with either rheumatoid arthritis (RA) or amyloidosis. Because symptoms of the two entities overlap, it can be difficult to address a potential dual diagnosis of FCAS and an autoimmune disorder. We found seven previously reported cases of FCAS and amyloidosis and five cases of FCAS and RA and present another case of an FCAS-RA dual diagnosis

Gallbladder containing incisional hernia in an elderly woman

Key Clinical Message Gallbladder herniation is a rare phenomenon with risk factors of being female, older age, and previous history of hernias. Imaging modalities can confirm the diagnosis. Cholecystectomy and hernia repair to prevent strangulation may be warranted

Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations

Germline loss-of-function mutations in the transcription factor signal transducer and activator of transcription 3 (STAT3) cause immunodeficiency, whereas somatic gain-of-function mutations in STAT3 are associated with large granular lymphocytic leukemic, myelodysplastic syndrome, and aplastic anemia. Recently, germline mutations in STAT3 have also been associated with autoimmune disease. Here, we report on 13 individuals from 10 families with lymphoproliferation and early-onset solid-organ autoimmunity associated with 9 different germline heterozygous mutations in STAT3. Patients exhibited a variety of clinical features, with most having lymphadenopathy, autoimmune cytopenias, multiorgan autoimmunity (lung, gastrointestinal, hepatic, and/or endocrine dysfunction), infections, and short stature. Functional analyses demonstrate that these mutations confer a gain-of-function in STAT3 leading to secondary defects in STAT5 and STAT1 phosphorylation and the regulatory T-cell compartment. Treatment targeting a cytokine pathway that signals through STAT3 led to clinical improvement in 1 patient, suggesting a potential therapeutic option for such patients. These results suggest that there is a broad range of autoimmunity caused by germline STAT3 gain-of-function mutations, and that hematologic autoimmunity is a major component of this newly described disorder. Some patients for this study were enrolled in a trial registered at www.clinicaltrials.gov as #NCT00001350