Disease activity and treatment efficacy using patient-level Psoriasis Area and Severity Index scores from tildrakizumab phase 3 clinical trials.

BACKGROUND: It is unclear whether primary efficacy outcomes in plaque psoriasis clinical trials represent residual disease during treatment. OBJECTIVES: To evaluate supplementing dichotomous efficacy with residual disease activity. METHODS: This post hoc analysis used pooled, patient-level data after tildrakizumab 100 mg (N = 616) or placebo (N = 309) treatment from reSURFACE 1/2 (NCT01722331/NCT01729754) phase 3 clinical trials of patients with moderate to severe plaque psoriasis. RESULTS: Median baseline Psoriasis Area and Severity Index (PASI) was 17.9 for patients receiving tildrakizumab 100 mg. At Week 12, median PASI was 2.9, whereas dichotomous PASI 90 response rate was 36.9%, and absolute PASI <5.0, <3.0, and <1.0 were 64.0%, 50.8%, and 23.3%, respectively. At Week 28, median PASI was 1.7, whereas PASI 90 response rate was 51.9%, and absolute PASI <5.0, <3.0, and <1.0 were 75.3%, 62.8%, and 38.0%, respectively. Dermatology Life Quality Index and PASI scores were correlated through Week 28 (r = 0.51, p ≤ .0001). CONCLUSIONS: Disease activity was more reliably estimated by PASI scores than percentage PASI improvement; this may partially explain efficacy disparities between clinical trials and practice. These results suggest supplementing dichotomous PASI improvement with PASI scores and consideration of patient treatment goals could facilitate clinical decisions.

Echolalia as a novel manifestation of neuropsychiatric systemic lupus erythematosus.

"That tongue of yours, by which I have been tricked, shall have its power curtailed and enjoy the briefest use of speech." With these words, Hera, of Greek mythology, deprived the nymph Echo of spontaneous speech, constraining her instead to merely repeating the words of others. Echolalia, which derives from the word "echo," is disordered speech in which an individual persistently repeats what is heard. Echolalia has been described in patients with a number of neuropsychiatric illnesses including autism and Tourette's syndrome. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a heterogeneous disease with protean manifestations that may occur in approximately 25% to 50% of patients with systemic lupus erythematosus (SLE). Although the most common manifestations include cognitive dysfunction (50%) and seizures (20%), NPSLE may also present as peripheral neuropathy (15%), psychosis (10%), or other central nervous system abnormalities. We report the case of a 57-year-old woman with SLE and echolalia.

Osseous disease in patients with pulmonary sarcoidosis and musculoskeletal symptoms.

Little is known about the clinical manifestations and correlates of osseous sarcoidosis and few data exist to guide pulmonologists in their evaluation of patients for possible osseous involvement. To determine the relationship between pulmonary and osseous sarcoidosis, and to develop an algorithm for use by pulmonologists in assessing patients with suspected osseous sarcoidosis, we conducted a retrospective, case control study of patients with pulmonary sarcoidosis and musculoskeletal complaints who were evaluated for osseous disease. All patients underwent a standard evaluation to include physical examination, chest radiograph (CXR), spirometry (PFTs), bone scintigraphy and plain radiographs of the hands and feet. Patients completed a health assessment questionnaire and serum angiotenisin converting enzyme, erythrocyte sedimentation rate, and C-reactive protein were measured. Patients eventually diagnosed with osseous sarcoidosis were compared to those lacking osseous involvement. Osseous involvement in patients with pulmonary sarcoidosis and musculoskeletal symptoms was common and seen in 38.9% of subjects. Patients with osseous sarcoidosis were more likely to concomitantly suffer from cutaneous sarcoidosis and to have elevated ACE levels and ESRs. No measure of pulmonary involvement (CXR stage, PFTs or symptoms) differentiated patients with osseous sarcoidosis from those without this condition. In cases of osseous sarcoidosis, bone scintigraphy identified a mean of four sites of osseous involvement, some of which would have been missed with the use of plain radiographs limited to the hands and feet. We conclude that in patients with pulmonary sarcoidosis who have significant musculoskeletal complaints, osseous involvement is frequent. Pulmonary features of sarcoidosis do not differ between patients with and without osseous disease. Bone scintigraphy aids in the evaluation of these patients.

The use of Western blotting as the confirmatory test for syphilis in patients with rheumatic disease.

OBJECTIVE: As a direct or indirect result of antiphospholipid antibody production, subjective laboratory interpretation, and false positive results, the common serologic tests for syphilis have been inherently inaccurate diagnostic tests in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases. We assessed the diagnostic accuracy of syphilis testing in patients with SLE and other autoimmune diseases using the treponemal Western blot (TWB) as the gold standard. METHODS: A prospective cohort study carried out at a tertiary care medical center. We studied 107 patients with autoimmune disease, 50 with at least one positive serologic test for syphilis and 57 disease matched controls. Prior to enrollment all eligible patients underwent a clinical assessment performed by at least 2 rheumatologists to confirm a diagnosis of rheumatic disease. All subjects underwent serologic testing, in blinded fashion, for syphilis using the rapid plasma reagin test (RPR), Venereal Disease Research Laboratory test (VDRL), fluorescent treponemal antibody absorption test (FTA-ABS), and the TWB. RESULTS: Eighty-seven percent of the patients studied were female, the mean age was 46.5 years, and the most common diagnosis at the time of enrollment was SLE. Using the TWB as the gold standard diagnostic test for syphilis, the sensitivity, specificity, and positive predictive values for each syphilis test were calculated. The sensitivity and specificity for the RPR in patients with rheumatic disease was 62.5% (95% confidence interval 24.5 to 91.5%) and 91.9% (95% CI 84.2 to 96.2%), respectively. The sensitivity and specificity for the VDRL were 37.5% (95% CI 8.5 to 75.5%) and 89.9% (95% CI 81.8 to 94.8%), respectively. Confirmatory syphilis testing using the FTA-ABS showed a sensitivity of 100% (95% CI 68.6 to 100%) and a specificity of 67.7% (95% CI 57.4 to 76.5%). Eight patients tested positive for syphilis by Western blotting. For the FTA-ABS test, there was a significantly higher number of false positive results (n = 32) compared to false negative results (n = 0), p < 0.0005. CONCLUSION: The FTA-ABS is not an accurate confirmatory test for syphilis in patients with SLE and other autoimmune diseases. While a negative FTA-ABS may exclude syphilis infection in the majority of cases, a positive FTA-ABS test result cannot assuredly confirm syphilis infection in this population. Western blotting is an accurate confirmatory test for syphilis and may be necessary to unequivocally discern the immunological response of syphilis from that of an underlying autoimmune disease.

Epinephrine-induced lactic acidosis in the setting of status asthmaticus.

A relationship between intravenous epinephrine infusion and the development of lactic acidosis has been well described. We report a temporal association between the administration of subcutaneous epinephrine and the development of lactic acidosis in the setting of status asthmaticus. A 20-year-old woman with a history of asthma came to the emergency service in acute respiratory distress and was treated with subcutaneous epinephrine. Six hours later, serial arterial blood gas studies revealed the onset of a primary metabolic acidosis. Additional diagnostic studies revealed a serum lactate level of 9.5 mumol/L. The lactic acidosis resolved within 15 hours. The patient never exhibited signs of hypotension, hypoxemia, or sepsis, and other potential etiologies for lactic acidosis were excluded. We believe the events of this case constitute a new observation and theorize a mechanism of peripheral vasoconstriction and transient tissue hypoperfusion mediated by the subcutaneous epinephrine.