Association of Race and Risk of Future Scleroderma Renal Crisis at Systemic Sclerosis Diagnosis.

OBJECTIVE: Scleroderma renal crisis (SRC) is a rare and severe manifestation of systemic sclerosis (SSc). Although it is well documented that Black patients with SSc have worse morbidity and mortality than non-Black patients, racial predilection for SRC is underreported. We examine the association of race and future development of SRC in an SSc cohort. METHODS: Using the electronic health record of the US Military Health System, we conducted a comprehensive chart review of each patient with SSc from 2005 to 2016. The final study cohort was comprised of 31 SRC cases and 322 SSc without SRC controls. We conducted logistic regression of SRC as the outcome variable and race (Black versus non-Black) as the primary predictor variable, adjusted for age, estimated glomerular filtration rate, hypertension, and proteinuria at SSc diagnosis. RESULTS: Of 353 patients, 294 had identifiable race (79 Black, 215 non-Black). Thirteen of 79 Black patients (16.5%) versus 16 of 215 (7.4%) non-Black patients developed SRC (P = 0.02). On adjusted analysis, Black patients had a significantly higher risk of developing SRC than non-Black patients (odds ratio 6.4 [95% confidence interval 1.3-31.2], P = 0.02). Anti-Ro antibody was present in a higher proportion of Black SRC patients versus Black patients without SRC (45% versus 14%, P = 0.01). Conversely, older age, thrombocytopenia, and anti-RNA polymerase III antibody at SSc diagnosis were significantly associated with future SRC in the non-Black cohort. CONCLUSION: Black race was independently associated with a higher risk of future SRC. Further studies are needed to elucidate the mechanisms that underlie this important association.

Autoantibodies are present before the clinical diagnosis of systemic sclerosis.

Systemic sclerosis (SSc) is a heterogeneous autoimmune disorder associated with vascular dysfunction and fibrotic changes in the skin, vasculature and internal organs. Although serologic abnormalities are an important diagnostic tool for SSc, little is known about whether autoantibodies precede clinical diagnosis. Here we investigated the presence of autoantibodies before SSc diagnosis and assessed whether certain autoantibodies might associate with the future onset of scleroderma renal crisis (SRC), a potentially fatal complication of the disease. Using the Department of Defense Serum Repository, autoantibodies were analyzed from archived, prospectively collected, longitudinal serum samples from sixteen individuals with SRC (SSc/SRC) and thirty cases of SSc without SRC (SSc/no SRC), matched for age, sex, and race. Seventy five percent (12/16) of the SSc/SRC and 40% (12/30) of the SSc/no SRC were seropositive for at least one autoantibody prior to clinical diagnosis (up to 27.1 years earlier, mean = -7.4 years). Although both disease groups demonstrated a heterogeneous immunoreactivity profile against the autoantigen panel, the SSc/SRC subjects showed two enriched clusters with one featuring elevated levels of autoantibodies against Ro52 and/or Ro60 and another with high levels of immunoreactivity against the RNA polymerase complex. Consistent with larger spectrum of immunoreactivity and the elevated levels of autoantibodies in SSc/SRC, the total response against the autoantigen panel from the last time point of the seropositive subjects revealed that the SSc/SRC cohort harbored higher antibody levels (p = 0.02) compared to SSc/no SRC. Overall, our findings demonstrate that relevant seropositive autoantibodies often precede the clinical diagnosis of SSc/no SRC and SSc/SRC.

Risk Factors for Future Scleroderma Renal Crisis at Systemic Sclerosis Diagnosis.

OBJECTIVE: Systemic sclerosis (SSc) is a disease of autoimmunity, fibrosis, and vasculopathy. Scleroderma renal crisis (SRC) is one of the most severe complications. Corticosteroid exposure, presence of anti-RNA polymerase III antibodies (ARA), skin thickness, and significant tendon friction rubs are among the known risk factors at SSc diagnosis for developing future SRC. Identification of additional clinical characteristics and laboratory findings could expand and improve the risk profile for future SRC at SSc diagnosis. METHODS: In this retrospective cohort study of the entire military electronic medical record between 2005 and 2016, we compared the demographics, clinical characteristics, and laboratory results at SSc diagnosis for 31 cases who developed SRC after SSc diagnosis to 322 SSc without SRC disease controls. RESULTS: After adjustment for potential confounding variables, at SSc diagnosis these conditions were all associated with future SRC: proteinuria (p < 0.001; OR 183, 95% CI 19.1-1750), anemia (p = 0.001; OR 9.9, 95% CI 2.7-36.2), hypertension (p < 0.001; OR 13.1, 95% CI 4.7-36.6), chronic kidney disease (p = 0.008; OR 20.7, 95% CI 2.2-190.7), elevated erythrocyte sedimentation rate (p < 0.001; OR 14.3, 95% CI 4.8-43.0), thrombocytopenia (p = 0.03; OR 7.0, 95% CI 1.2-42.7), hypothyroidism (p = 0.01; OR 2.8, 95% CI 1.2-6.7), Anti-Ro antibody seropositivity (p = 0.003; OR 3.9, 95% CI 1.6-9.8), and ARA (p = 0.02; OR 4.1, 95% CI 1.2-13.8). Three or more of these risk factors present at SSc diagnosis was sensitive (77%) and highly specific (97%) for future SRC. No SSc without SRC disease controls had ≥ 4 risk factors. CONCLUSION: In this SSc cohort, we present a panel of risk factors for future SRC. These patients may benefit from close observation of blood pressure, proteinuria, and estimated glomerular filtration rate, for earlier SRC identification and intervention. Future prospective therapeutic studies could focus specifically on this high-risk population.

Novel use of rituximab in macrophage activation syndrome secondary to systemic lupus erythematosus.

Macrophage activation syndrome (MAS) is a rare disease characterised by aberrant immune hyperactivation of T lymphocytes and macrophages driven by cytokine dysfunction. The HLH-2004 protocol is commonly used for the treatment of MAS, but significant toxicities are associated. We describe a case of MAS secondary to systemic lupus erythematosus in a young female that responded well to rituximab in lieu of etoposide. She continues to be in remission 1 year following the completion of rituximab infusion and is maintained on hydroxychloroquine. This case highlights the need for further research on the use of rituximab and other available biologics in the setting of MAS in order to help guide further alternative treatment decisions.

Foreign body synovitis in the Pacific.

Foreign body synovitis in the Pacific region typically involves a penetrating injury to a joint. The introduced biomaterial produces an inflammatory reaction or innoculates the tissue with bacteria, creating an infection. Each year millions of people visit the Hawaiian Islands to hike, surf, snorkel, and participate in other outdoor activities, creating an array of interactions between people and nature. The two most commonly reported penetrating foreign body joint injuries are sea urchin synovitis and synovitis due to implantation of organic material such as wood splinters or plant thorns. In this article we describe the presentation, infectious profile, and treatment of these joint injuries.

Lupus erythematosus tumidus: a unique disease entity.

Lupus erythematosus tumidus (LET) is a photosensitive skin disease characterized by succulent, edematous, and non-scarring plaques. Histologic features include perivascular and periadnexal lymphocytic infiltration and interstitial mucin deposition. Despite being first described in 1909, there are few case reports in the current literature describing this disease and even fewer that discuss treatment. We describe a case of a 22-year-old woman with systemic lupus erythematosus (SLE) and secondary class V lupus nephritis. She was referred to Dermatology for an intermittent pruritic facial eruption that was clinically and histologically consistent with LET. There is much controversy in literature as to whether or not LET is a unique variant of cutaneous lupus erythematosus. Interestingly, the mainstay of treatment for LET, in the limited case reports and series that exist, is with antimalarial drugs, which our patient had already been taking for SLE. This case exemplifies the need for complete disease characterization, evidence-based treatment, and a multidisciplinary approach.

A surprising cause of acute right upper quadrant pain.

A 42 year-old African-American woman was admitted for severe acute right upper quadrant pain. Her liver function tests showed a cholestatic pattern of hepatitis. She had no known history of liver disease or sarcoidosis. Imaging of her liver and biliary tree did not reveal any apparent cause for her right upper quadrant pain. A liver biopsy was performed which showed granulomatous disease. This prompted a CT chest that showed mediastinal lymphadenopathy. Biopsy of the mediastinal lymphnode revealed non-caseating granulomas. Despite having no pulmonary symptoms or history of pulmonary sarcoidosis, she was diagnosed with systemic pulmonary sarcoidosis. She was treated with corticosteroids and had complete resolution of symptoms over the next several weeks.

Increased serum creatine phosphokinase in a child with bruising due to physical abuse.

Bruising is a frequent and often sentinel injury in children who are victims of physical abuse. Children who are evaluated in an emergency department for bruising, which may be due to abuse, present a challenge to physicians; the injuries themselves are medically minor and their severity can only be described qualitatively with photographs. Nonetheless, bruising in an infant or bruising in unusual locations in young children can indicate violence and risk. These children also present a challenge to the Child Protective Services system because the injuries generally resolve quickly without medical treatment and do not result in long-term sequelae. Creatine phosphokinase (CPK) is released from injured muscle and results in increased serum CPK concentrations. We report on a case of isolated bruising due to child physical abuse in which serum CPK concentrations were markedly increased, demonstrating clinically unsuspected rhabdomyolysis. The increased serum CPK concentrations provided important quantitative information about the seriousness of the bruising. A subsequent chart review of children evaluated by our hospital's child protection team for isolated bruising during a 6-year period demonstrated that there were other children with bruising due to abuse who also had increased serum CPK concentrations. This information suggests that increased serum CPK in children with bruising due to abuse may be more common than previously thought and that this information may have the potential to be used to provide quantitative, objective information about the seriousness of the bruising. We recommend that physicians consider measuring serum CPK in children with bruising due to physical abuse.