An Exuberant Case of Ulceronodular-Rupioid (Malignant) Syphilis in an HIV Patient: A Proposal for New Diagnostic Criteria.

We report the case of a 28-year-old male with uncontrolled human immunodeficiency virus (HIV) infection who presented with extensive ulcerated lesions with dark lamellated crusting on his face, torso, and limbs. The patient had a rapid plasma reagin (RPR) titer of 1:512, indicative of syphilis. A skin biopsy revealed granulomata surrounded by lymphocytes, histiocytes, and plasma cells, with spirochetes visible on immunohistochemical staining. The patient's rash resolved with hyperpigmented scarring after penicillin and doxycycline treatment. This severe form of secondary syphilis has been termed malignant syphilis, lues maligna, ulceronodular syphilis, or rupioid syphilis. We propose a single descriptive name for this entity, ulceronodular-rupioid syphilis. In 1969, Fisher proposed criteria for malignant syphilis based on lesion appearance, histopathologic findings, high RPR values, and rapid response to treatment. We found that the Fisher criteria were imprecise with respect to specific histopathologic findings, the quantitation of RPR values, and what constitutes rapid response to treatment. Thus, we examined an additional 74 cases from the literature and propose new diagnostic criteria based on rash appearance, histopathologic characteristics, non-treponemal and treponemal test positivity, and response to therapy. We also found that uncontrolled viremia, and not a low CD4 count, is a major risk factor for ulceronodular-rupioid syphilis in HIV patients.

Cytokine and T cell responses in post-chikungunya viral arthritis: A cross-sectional study.

OBJECTIVE: To define the relationship between chronic chikungunya post-viral arthritis disease severity, cytokine response and T cell subsets in order to identify potential targets for therapy. METHODS: Participants with chikungunya arthritis were recruited from Colombia from 2019-2021. Arthritis disease severity was quantified using the Disease Activity Score-28 and an Arthritis-Flare Questionnaire adapted for chikungunya arthritis. Plasma cytokine concentrations (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood T cell subsets were measured using flow cytometry. RESULTS: Among participants with chikungunya arthritis (N = 158), IL-2 levels and frequency of regulatory T cells (Tregs) were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 (p<0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p<0.05) without affecting T effector (Teff) frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4+ T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p<0.05). CONCLUSION: Chikungunya arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers. Future research may consider targeting these pathways for therapy.