Role of NLRP3 inflammasome in diabetes and COVID-19 role of NLRP3 inflammasome in the pathogenesis and treatment of COVID-19 and diabetes NLRP3 inflammasome in diabetes and COVID-19 intervention.

2019 Coronavirus Disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A "cytokine storm", i.e., elevated levels of pro-inflammatory cytokines in the bloodstream, has been observed in severe cases of COVID-19. Normally, activation of the nucleotide-binding oligomeric domain-like receptor containing pyrin domain 3 (NLRP3) inflammatory vesicles induces cytokine production as an inflammatory response to viral infection. Recent studies have found an increased severity of necrobiosis infection in diabetic patients, and data from several countries have shown higher morbidity and mortality of necrobiosis in people with chronic metabolic diseases such as diabetes. In addition, COVID-19 may also predispose infected individuals to hyperglycemia. Therefore, in this review, we explore the potential relationship between NLRP3 inflammatory vesicles in diabetes and COVID-19. In contrast, we review the cellular/molecular mechanisms by which SARS-CoV-2 infection activates NLRP3 inflammatory vesicles. Finally, we propose several promising targeted NLRP3 inflammatory vesicle inhibitors with the aim of providing a basis for NLRP3-targeted drugs in diabetes combined with noncoronary pneumonia in the clinical management of patients.

Diagnostic ambiguity of aseptic necrobiosis of a uterine fibroid in a term pregnancy: a case report.

BACKGROUND: Uterine fibroids are the most common uterine tumours in females of reproductive age. During pregnancy, uterine fibroids may be complicated by aseptic necrobiosis. We herein report an ambiguous clinical presentation of uterine fibroids in pregnancy and discuss the diagnostic challenges encountered in our resource-constraint setting. CASE PRESENTATION: A term pregnant Cameroonian woman was admitted to our maternity unit with clinical findings suggestive of a strangulated umbilical hernia. She underwent an emergency caesarean section which fortuitously revealed aseptic necrobiosis of a uterine fibroid, managed within the same surgical intervention by myomectomy. Her post-operative course was uneventful. CONCLUSION: The authors highlight the need for a high index of suspicion by healthcare providers, as well as the need for a multidisciplinary approach for a favourable maternal and foetal outcome.

Primary Necrobiotic Xanthogranulomatous Sialadenitis with Submandibular Gland Localization without Skin Involvement

Necrobiotic xanthogranulomatous reaction is a multiorgan, non-Langerhans cell histiocytosis with an unknown etiology. Occurrence in the salivary gland is extremely rare. We recently identified a case of necrobiotic xanthogranulomatous sialadenitis in a 73-year-old Korean woman who presented with a painless palpable lesion in the chin. There was no accompanying cutaneous lesion. Partial resection and subsequent wide excision with neck dissection were performed. Pathological examination showed a severe inflammatory lesion that included foamy macrophages centrally admixed with neutrophils, eosinophils, lymphocytes, plasma cells, and scattered giant cells, as well as necrobiosis. During the 12-month postoperative period, no grossly remarkable change in size was noted. Necrobiotic xanthogranulomatous inflammation may be preceded by or combined with hematologic malignancy. Although rare, clinicians and radiologists should be aware that an adhesive necrobiotic xanthogranuloma in the salivary gland may present with a mass-like lesion. Further evaluation for hematologic disease and close follow-up are needed when a pathologic diagnosis is made.

Necrotizing meningoencephalitis caused by Sarcocystis falcatula in bare-faced ibis (Phimosus infuscatus).

The infection by S. falcatula is commonly associated with respiratory disease in captive psittacine birds, with a few case reports of this protozoan causing encephalitis in wild birds. We describe the clinical, pathological, and molecular aspects of an infection by S. falcatula in a bare-faced ibis (Phimosus infuscatus). Clinically, wing paralysis and mild motor incoordination were observed. At necropsy, the telencephalic cortex showed multifocal to coalescing yellowish soft areas. Histologically, multifocal to coalescent nonsuppurative necrotizing meningoencephalitis of telencephalic cortex, cerebellum, and brainstem was observed. Necrotic areas showed multiple protozoan organism characteristics of Sarcocystis sp. schizonts in the cytoplasm of endothelial cells or lying free in the neuropil. Partial genetic sequences of the gene encoding cytochrome b (CYTB), the gene encoding the beta subunit of RNA polymerase (RPOB) and the first internal transcribed spacer (ITS-1) from Sarcocystis sp. schizonts revealed that the parasite had ITS-1 sequences that were 100% identical to the homologous alleles from Sarcocystis sp. shed by Didelphis albiventris in Brazil. RPOB and CYTB sequences were 100% identical to homologous of S. falcatula available in Genbank. Thus, this is the first report of necrotizing meningoencephalitis caused by S. falcatula in bare-faced ibis (P. infuscatus).

Necrólisis tóxica epidérmica inducida por cotrimoxazol / Epidermic toxic necrolysis induced by co-trimoxazole

Se describe el caso clínico de una paciente de 60 años de edad con antecedentes de hipertensión arterial, por lo cual llevaba tratamiento con nifedipino, quien asistió al Cuerpo de Guardia del Hospital General Docente Orlando Pantoja Tamayo en el municipio de Contramaestre, Santiago de Cuba, por presentar deposiciones diarreicas, vómitos, hipertermia (38 0C) y lesiones generalizadas en la piel en forma de pústulas eritemato-costrosas con flictenas y dolor. La paciente refirió que solía automedicarse con cotrimoxazol por la reiteración de infecciones urinarias y que desde hacía 3 días estaba consumiendo dicho medicamento. El estudio histopatológico mostró una necrólisis tóxica epidérmica (síndrome de Lyell). A pesar de los cuidados médicos, evolucionó desfavorablemente y se complicó con una insuficiencia renal aguda, lo que le condujo a la muerte(AU)

The case report of a 60 years patient with a history of hypertension, reason why she had treatment with nifedipine, who went to the Emergency Room of Orlando Pantoja Tamayo Teaching General Hospital in Contramaestre, Santiago de Cuba, due to diarrheical stools, vomits, hyperthermia (38 0C) and generalized skin injuries in the type of erythemato-scabby pustules with flictenas and pain is described. The patient referred that she was accustomed to self-medication with co-trimoxazole due to repeated urinary infections and that she was consuming this medication for 3 days. The pathological study showed an epidermic toxic necrolysis (Lyell syndrome). In spite of the medical cares, she had an unfavorable clinical course and she complicated with an acute renal failure, leading to death(AU)

[Cutaneous granulomatosis]. / Granulomatoses cutanées.

Granulomatous skin diseases represent a large group of reactive dermatoses occurring in response to different stimuli and whose skin biopsy is characterized by a granulomatous inflammatory infiltrate. By their very heterogeneous clinical presentation, it seems difficult to distinguish them and make their diagnosis. Clinically, it may be useful to separate localized forms of disseminated forms of cutaneous granulomatosis, although this distinction is often artificial. We will discuss here the main forms of localized and disseminated cutaneous granulomatosis, and, in light of recent literature data, mention different therapeutic options in each case.

Cutaneous necrobiotic conditions associated with rheumatoid arthritis: important extra-articular involvement.

Rheumatoid arthritis (RA) presents with various skin conditions as extra-articular manifestations. Rheumatoid nodule is the representative specific skin lesion, histologically exhibiting central necrosis (necrobiosis) surrounded by palisaded macrophages, and being further perivascularly infiltrated with inflammatory cells in the outer regions. Also, there are several skin lesions which histologically show necrobiotic conditions with altered connective tissue degeneration. Necrobiosis may be closely associated with the pathogenesis of RA, i.e., collagen degeneration, recruitment of activated neutrophils, production of various cytokines, and vascular injury. On the other hand, rheumatoid nodule is suggested to develop during therapies with certain drugs such as methotrexate and biologics. These findings may be a clue to understanding the pathomechanisms of rheumatoid nodules. This paper describes several necrobiotic conditions associated with RA, and also discusses the possible pathogenesis and differential diagnosis of rheumatoid nodules. Necrobiosis is the major pathologic condition of cutaneous involvement associated with RA.

Palisaded neutrophilic and granulomatous dermatitis in association with subcutaneous nodular and systemic sarcoidosis.

Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare entity that has been clearly defined neither clinically nor histopathologically. PNGD has been associated with some immune-mediated disorders such as rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, Behçet's disease, as well as with lymphoproliferative conditions, bacterial endocarditis, sarcoidosis, and various drugs. We present a 44-year-old Caucasian woman with roundish erythematous-livid plaque and erythematous papules on the left calf that were present for three months. Histopathology of plaque lesion showed palisading neutrophilic and granulomatous dermatitis. Subsequently, she developed a firm and tender nodule on the right calf. Histopathology of the nodule showed typical naked sarcoid granulomas in the dermis and subcutis. Additionally, the patient developed non-tender subcutaneous nodules on the cheeks, submandibular region and left breast with normal overlying skin, which were histopathologically diagnosed as sarcoid granuloma. Red eyes and lower visual acuity on the right eye were diagnosed as anterior uveitis. Therefore, systemic sarcoidosis was established. This is a case of PNGD described in an adult patient with sarcoidosis with cutaneous, breast, eye and lung involvement established by clinical, radiographic, laboratory, and histopathologic criteria.

Necrobiosis Lipoidica Presenting as Unilateral Papulovesicular Eruptions on the Lower Leg / 대한피부과학회지

Necrobiosis lipoidica is a chronic granulomatous disease that has a well-known association with diabetes mellitus. It usually affects the bilateral lower legs of middle-aged women. Over time, the clinical features vary from red-brown papules to sharply demarcated yellow-brown plaque with atrophic center. Some of the lesions may become ulcerated, especially in diabetic patients. A 61-year-old Korean female with a history of diabetes, ischemic heart disease, and pancreatic cancer was referred to our clinic for evaluation of the painful papulovesicles on her left lower leg. Under the assumptive diagnosis of herpes zoster, we immediately started an antiviral agent. However, her skin lesions rapidly increased in size and in number, and progressed to the multiple ulcerations in 9 days. Histopathologic examination showed several poorly circumscribed necrobiotic granulomas in the deep dermis and subcutis levels of the skin. In addition, prominent vascular ectasia and vasculitis were observed. We diagnosed the patient as having necrobiotic lipoidica, and treated her with oral dapsone, colchicine, phentoxifylline and antiplatelets. Her leg ulcerations healed after four weeks of treatment.