サルコイドーシス

Multicentric reticulohistiocytosis (MRH) is a rare non-Langerhans cell histiocytosis characterized by destructive polyarthritis and papulonodular cutaneous lesions. We describe a woman who developed erythroderma 20 years after MRH diagnosis-to our knowledge, a previously unreported manifestation of this disease. The patient initially presented at age 50 with arthralgia, and MRH was diagnosed one year later based on distal interphalangeal (DIP) joint deformities, erythematous papules on the lower legs, and a skin biopsy showing dermal infiltration of CD68-positive, S-100- and CD1a-negative histiocyte-like cells with ground-glass eosinophilic cytoplasm. Despite long-term treatment with methotrexate (MTX), prednisolone (PSL), infliximab (year 11), and bone-modifying agents (alendronate, later denosumab), the disease progressed, with development of pulmonary arterial hypertension (PAH) attributable to lesions around the upper pulmonary veins. At age 71, twenty years after diagnosis, pruritic erythema appeared on the back and evolved into erythroderma despite topical corticosteroids. Biopsies from erythematous areas demonstrated CD68-positive histiocytic infiltrate identical to that of the original MRH lesions, whereas biopsies from clinically uninvolved skin showed no such infiltration, supporting a direct association with the MRH disease process. Comprehensive evaluation excluded eczematous/atopic erythroderma (normal eosinophils and IgE), drug-induced erythroderma (no new medications; infliximab discontinued 9 years previously), dermatophytosis (negative PAS staining), granulomatous mycosis fungoides (absent characteristic histological features), sarcoidosis (normal sIL-2R; no granulomas on biopsy), dermatomyositis (absent characteristic features; normal creatine kinase), and internal malignancy (contrast-enhanced CT and 2-year follow-up). MTX was discontinued because of MTX-induced interstitial pneumonia, and oral PSL was increased to 30 mg/day, with rapid improvement; the patient is currently maintained on PSL 10 mg/day without relapse. The cumulative inflammatory burden of long-standing MRH may have culminated in this erythrodermic phenotype.

Background and AimBleomycin is a cytotoxic antibiotic mainly used for the treatment of carcinoma of the ovary, skin, cervix, vagina, vulva, and penis, as well as malignant lymphoma and testicular cancer. Assessing the real-world safety of bleomycin, particularly in the treatment of ovarian cancer, is essential because of its widespread clinical application. Further investigation of its risk profile in patients with ovarian cancer remains critically important.MethodsThis retrospective, observational pharmacovigilance study was based on data from the Food and Drug Administration Adverse Event Reporting System database. Data were collected from the Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the third quarter of 2024. The reporting odds ratio, proportional reporting ratio, multi-item gamma Poisson shrinker, and Bayesian confidence propagation neural network were used for disproportionality analyses of adverse events related to bleomycin. Additionally, the Weibull distribution was used to model the risk of adverse events over time.ResultsAdverse reactions listed on the official drug label, such as febrile neutropenia, pulmonary toxicity, and respiratory failure, exhibited positive signals. The investigation also identified additional safety concerns not included in the product information, including disseminated intravascular coagulation, acute myeloid leukemia, growing teratoma syndrome, shock, hyperthyroidism, and sarcoidosis. Close surveillance of treatment-related complications, especially during the initial 30 days of therapy, is strongly recommended.ConclusionsOur results are consistent with clinical observations and reveal the emergence of previously unreported adverse event signals associated with bleomycin, along with their demographic and time-to-onset characteristics. Additional population-based medication research is needed to validate these findings.

Sarcoidosis is a heterogeneous, multisystem granulomatous disorder of unknown etiology that predominantly affects adults aged 20-60 years. Clinical presentation ranges from asymptomatic disease detected incidentally to progressive organ dysfunction. The lymphatic system, lungs, and skin are most commonly involved, although virtually any organ may be affected. Diagnosis remains challenging due to the absence of a pathognomonic test and significant overlap with infectious, autoimmune, and neoplastic conditions, necessitating careful evaluation to exclude alternative etiologies. Accordingly, sarcoidosis remains a diagnosis of exclusion, supported by compatible clinical and radiographic findings and histologic evidence of non-necrotizing granulomas. This review summarizes current understanding of sarcoidosis epidemiology, immunopathogenesis, and clinical manifestations, and provides a practical approach to diagnosis and management. It also highlights recent advances, including key clinical trials, emerging biomarkers, and novel therapeutic strategies. Finally, it addresses common clinical challenges and persistent knowledge gaps in the field. The goal is to inform clinicians with an updated framework to optimize care for patients with sarcoidosis.

BACKGROUND: End user co-design in the personal digital health technology space is underdeveloped. Clinical uptake of personal digital health technologies has been poor, highlighting a need to cocreate solutions with end users. OBJECTIVE: The study aimed to describe an "end user" co-design framework in the development of 5 prototype personal health apps for patients with different rare or complex diseases. METHODS: A patient-led, user-centered, collaborative personal health app plus wearable plug-in co-design methodology was developed. Five prototype apps were developed for end users with long COVID-19, pancreatitis, primary ciliary dyskinesia, sarcoidosis, and valosin-containing protein disease by a multidisciplinary partnership including patients, app design and development experts, user experience experts, clinicians, and patient-driven organizations. Phase 1 involved a 6-month co-design process with 5 modules involving patient-driven organizations that included the codevelopment of specifications through group workshops and independent exercises that defined the goals, content, features, and user experience of each app. Phase 2 involved app build-out, internal alpha testing, and beta study preparations. Phase 3 involved a usability beta testing study in which end users used the app and associated wearable/smart devices (Oura ring, Lumia ear device, Empatica EmbracePlus, and MIR Spirobank Spirometer) for up to 5 months. Participant feedback was documented continuously and systematically, centering on the following themes: functionality, usability, harms, benefits, self-explorations, and beta testing study details related to retention and adherence. RESULTS: While unique app goals were codeveloped by each disease group, a central goal across groups was to develop a personal health app enabling users to track subjective, self-reported symptoms, objective measures of health, and unique modifiers of symptoms. A total of 239 end user participants participated in the beta testing pilot study. Enrollment and retention rates were high, ranging from 94% to 100% and 92.2% to 100%, respectively. All active participants gave some form of feedback: there were 257 unique participant suggestions of how to specifically modify or improve the study app experience. Participant feedback themes commonly centered around customization to reduce daily burden and improve personal tailoring of the app. Participants' desires surrounding symptom displays were heterogeneous. CONCLUSIONS: Personal health app co-design is rooted in a complex digital landscape that requires a significant amount of up-front effort and time. However, the up-front investment of time can result in rich and diverse end user feedback that could save time in the app development trajectory to implementation. This paper provides a co-design framework and the building blocks of 5 prototype personal health apps with publicly available open-source code on GitHub. These prototypes could be leveraged for improving understanding of, communicating symptoms of, and providing n-of-1 suggestions for rare or complex diseases, providing benefit to patient communities and individual patients.