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Dermatologie (Heidelberg, Germany) Dec 2022A 50-year-old female farmer was initially diagnosed with generalized granuloma annulare and treated with local steroids and ultraviolet (UV) light therapy for...
A 50-year-old female farmer was initially diagnosed with generalized granuloma annulare and treated with local steroids and ultraviolet (UV) light therapy for 10 years, albeit without success. A histopathological examination in our clinic changed the diagnosis to Wells' syndrome, based on the typical findings of eosinophilic cellulitis together with flame figures. A systemic approach with pulse steroid therapy resulted in complete remission of pruritus and skin manifestations. This case demonstrates successful treatment of a patient with eosinophilic cellulitis.
Topics: Female; Humans; Middle Aged; Eosinophils; Skin; Cellulitis; Pruritus
PubMed: 37728797
DOI: 10.1007/s00105-023-05216-4 -
European Journal of Medicinal Chemistry Dec 2023Perforin is a pore-forming protein whose normal function enables cytotoxic T and natural killer (NK) cells to kill virus-infected and transformed cells. Conversely,...
Perforin is a pore-forming protein whose normal function enables cytotoxic T and natural killer (NK) cells to kill virus-infected and transformed cells. Conversely, unwanted perforin activity can also result in auto-immune attack, graft rejection and aberrant responses to pathogens. Perforin is critical for the function of the granule exocytosis cell death pathway and is therefore a target for drug development. In this study, by screening a fragment library using NMR and surface plasmon resonance, we identified 4,4-diaminodiphenyl sulfone (dapsone) as a perforin ligand. We also found that dapsone has modest (mM) inhibitory activity of perforin lytic activity in a red blood cell lysis assay in vitro. Sequential modification of this lead fragment, guided by structural knowledge of the ligand binding site and binding pose, and supported by SPR and ligand-detected F NMR, enabled the design of nanomolar inhibitors of the cytolytic activity of intact NK cells against various tumour cell targets. Interestingly, the ligands we developed were largely inert with respect to direct perforin-mediated red blood cell lysis but were very potent in the context of perforin's action on delivering granzymes in the immune synapse, the context in which it functions physiologically. Our work indicates that a fragment-based, structure-guided drug discovery strategy can be used to identify novel ligands that bind perforin. Moreover, these molecules have superior physicochemical properties and solubility compared to previous generations of perforin ligands.
Topics: Perforin; Ligands; Killer Cells, Natural; Cell Death; Dapsone
PubMed: 37716187
DOI: 10.1016/j.ejmech.2023.115786 -
Critical Care Science 2023
Topics: Humans; Child; Dapsone; Methemoglobinemia
PubMed: 37712815
DOI: 10.5935/2965-2774.20230018-en -
Annals of the Rheumatic Diseases Jan 2024Secukinumab is monoclonal antibody that targets interleukin 17 (IL-17) for treatment of psoriatic arthritis, psoriasis, and ankylosing spondylitis. We herein present a...
Secukinumab is monoclonal antibody that targets interleukin 17 (IL-17) for treatment of psoriatic arthritis, psoriasis, and ankylosing spondylitis. We herein present a psoriatic arthritis patient who developed leukocytoclastic vasculitis (LCV) following treatment with secukinumab. Genetic studies identified amino acid changes in two different IL-17 receptors, IL-17RA and IL-17-RC, and interacting DOCK8, Rab27A, and STX1 proteins. LCV completely resolved after withdrawal of the drug, transient treatment with dapsone and methylprednisolone, and switching to long-term therapy to IL-23 inhibitor tildrakizumab. This case reveals potential molecular bases of disease pathogenesis, intolerance of IL-17 blockade, and responsiveness to IL-23 inhibition in psoriatic arthritis.
Topics: Humans; Arthritis, Psoriatic; Interleukin-17; Antibodies, Monoclonal, Humanized; Vasculitis, Leukocytoclastic, Cutaneous; Interleukin-23; Psoriasis
PubMed: 37679036
DOI: 10.1136/ard-2023-224604 -
Cureus Aug 2023We present the case of a 37-year-old Haitian male who presented with a seven-month history of skin lesions on his face and extremities, weight loss, intermittent chills,...
We present the case of a 37-year-old Haitian male who presented with a seven-month history of skin lesions on his face and extremities, weight loss, intermittent chills, difficulty in breathing, and bilateral paresthesias in his feet. The lesions were most prominent on the pinnae of the ears. Biopsy of the lesions revealed large, rounded granulomatous infiltrates and histiocytes. Acid fast (Ziehl-Neelsen technique) and Kinyoun stains were positive for numerous acid-fast mycobacteria within the histiocytes. A polymerase chain reaction (PCR) was positive for which confirmed a diagnosis of lepromatous leprosy. Further analysis revealed positive purified protein derivatives (PPD) and QuantiFERON-TB™ test (QIAGEN, Hilden, Germany) with negative chest x-ray and sputum cultures. Labs also revealed vitamin D and G6PD (glucose-6-phosphate-dehydrogenasedeficiency. The patient was started on a combined therapy regimen of rifampin, moxifloxacin, and minocycline. In addition, he was started on vitamin D supplementation. After undergoing treatment for one year, there was notable regression of the patient's cutaneous lesions. Treatment is planned to continue for a total of 24 months. This case exemplifies the successful treatment of Hansen's disease in a patient with a G6PD deficiency. The patient's G6PD deficiency required avoidance of dapsone, which is typically used in the treatment of Hansen's disease. Furthermore, the patient's positive PPD and QuantiFERON-TB tests led to a delay in the treatment in order to rule out active tuberculosis. Left untreated, Hansen's disease has a high morbidity risk. Treatment regimens require careful consideration of coexisting comorbidities.
PubMed: 37664264
DOI: 10.7759/cureus.42816 -
SAGE Open Medical Case Reports 2023This case report describes the first known successful treatment of exfoliative cheilitis with the interleukin-4 receptor alpha antagonist dupilumab in an adult patient....
This case report describes the first known successful treatment of exfoliative cheilitis with the interleukin-4 receptor alpha antagonist dupilumab in an adult patient. With no response to topical tacrolimus, hydrocortisone, dapsone, crisaborole or systemic doxycycline, low dose isotretinoin, or methotrexate, she had resolution with off-label dupilumab after 4 months of treatment.
PubMed: 37560382
DOI: 10.1177/2050313X231193076 -
The Journal of Dermatological Treatment Dec 2023Schnitzler syndrome (SchS) is a rare autoimmune and inflammatory disease mediated by interleukin-1 beta (IL-1β). Recurrent monoclonal gammopathy and chronic urticarial...
Schnitzler syndrome (SchS) is a rare autoimmune and inflammatory disease mediated by interleukin-1 beta (IL-1β). Recurrent monoclonal gammopathy and chronic urticarial rash are the symptoms required for diagnosis according to the Strasbourg criteria. The low prevalence of this syndrome (around 300 cases have been reported) and confusion with other inflammatory disorders may delay the diagnosis for up to 5 years. Although the most effective treatment for SchS is anakinra, some patients do not respond to this treatment. We report a case of SchS in a 64-year-old woman with multiple episodes of fever, severe rash, erythema, arthralgia and dyspnea. The patient was successfully treated with canakinumab after anakinra intolerance and failure of colchicine, prednisone, methotrexate and dapsone. After the first dose of canakinumab the skin wounds rapidly improved and the patient did not require any concomitant treatments. The cause of SchS is still unknown and a differential diagnosis is recommended, especially with adult-onset Still´s disease due to their similar symptoms. Canakinumab, a specific anti-IL-1β antibody, blocks its binding to receptors, thereby preventing IL-1β-induced gene activation and production of inflammatory mediators. Canakinumab has proven to be an effective drug in SchS, providing an alternative to anakinra.
Topics: Adult; Female; Humans; Middle Aged; Schnitzler Syndrome; Interleukin 1 Receptor Antagonist Protein; Antibodies, Monoclonal, Humanized; Exanthema
PubMed: 37551725
DOI: 10.1080/09546634.2023.2242705 -
Indian Dermatology Online Journal 2023
PubMed: 37521218
DOI: 10.4103/idoj.idoj_380_22 -
Frontiers in Immunology 2023Epidermolysis bullosa acquisita (EBA) is a chronic, recurrent autoimmune subepidermal bullous disease characterized by the presence of autoantibodies targeting type VII... (Review)
Review
Epidermolysis bullosa acquisita (EBA) is a chronic, recurrent autoimmune subepidermal bullous disease characterized by the presence of autoantibodies targeting type VII collagen -- basement membrane zone antigen. Standard therapy for EBA includes a combination of systemic corticosteroids and dapsone; however, severe cases may require advanced treatment. The current article reports on four EBA cases in which biologics: infliximab, rituximab (Rtx), and intravenous immunoglobulin (IVIG) were applied. All patients fulfilled the clinical and immunological criteria of EBA: they presented tense blisters healing with atrophic scars on the skin on traumatized areas and in mucous membranes. The diagnosis of EBA was established using numerous techniques: direct and indirect immunofluorescence, salt split skin, ELISA, Fluorescence Overlay Antigen Mapping using Laser Scanning Confocal Microscopy. Since all the patients did not achieve long-term remission on standard treatment (prednisone, dapsone) due to ineffectiveness or side effects of drugs, they eventually were treated with biologics leading to extraordinary skin improvement and stopping the disease for 1-3 years. Biologics in all patients were tolerated very well. No side effects were observed during application as well as multi-month follow-up. The presented cases provide a premise that biological drugs can be a valuable component of EBA therapy.
Topics: Humans; Epidermolysis Bullosa Acquisita; Blister; Autoantibodies; Dapsone; Biological Products
PubMed: 37503352
DOI: 10.3389/fimmu.2023.1214011