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International Journal of Women's... Jun 2021Urticarial vasculitis is a rare clinicopathologic entity that is characterized by chronic or recurrent episodes of urticarial lesions. Skin findings of this disease can... (Review)
Review
Urticarial vasculitis is a rare clinicopathologic entity that is characterized by chronic or recurrent episodes of urticarial lesions. Skin findings of this disease can be difficult to distinguish visually from those of chronic idiopathic urticaria but are unique in that individual lesions persist for ≥24 hours and can leave behind dusky hyperpigmentation. This disease is most often idiopathic but has been linked to certain drugs, infections, autoimmune connective disease, myelodysplastic disorders, and malignancies. More recently, some authors have reported associations between urticarial vasculitis and COVID-19, as well as influenza A/H1N1 infection. Urticarial vasculitis can extend systemically as well, most often affecting the musculoskeletal, renal, pulmonary, gastrointestinal, and ocular systems. Features of leukocytoclastic vasculitis seen on histopathologic examination are diagnostic of this disease, but not always seen. In practice, antibiotics, dapsone, colchicine, and hydroxychloroquine are popular first-line therapies, especially for mild cutaneous disease. In more severe cases, immunosuppressives, including methotrexate, mycophenolate mofetil, azathioprine, and cyclosporine, as well as corticosteroids, may be necessary for control. More recently, select biologic therapies, including rituximab, omalizumab, and interleukin-1 inhibitors have shown promise for the treatment of recalcitrant or refractory cases.
PubMed: 34222586
DOI: 10.1016/j.ijwd.2021.01.021 -
Anais Brasileiros de Dermatologia 2022Epidermolysis bullosa acquisita is a rare autoimmune disease, characterized by the synthesis of anti-collagen VII autoantibodies, the main component of hemidesmosome...
Epidermolysis bullosa acquisita is a rare autoimmune disease, characterized by the synthesis of anti-collagen VII autoantibodies, the main component of hemidesmosome anchoring fibrils. The antigen-antibody binding elicits a complex inflammatory response, which culminates in the loss of dermo-epidermal adhesion of the skin and/or mucous membranes. Skin fragility with bullae, erosions, and milia in areas of trauma characterizes the mechanobullous form of the disease. In the inflammatory form of epidermolysis bullosa acquisita, urticarial inflammatory plaques with tense bullae, similar to bullous pemphigoid, or mucosal lesions can determine permanent scars and loss of functionality in the ocular, oral, esophageal, and urogenital regions. Due to the similarity of the clinical findings of epidermolysis bullosa acquisita with other diseases of the pemphigoid group and with porphyria cutanea tarda, the diagnosis is currently confirmed mainly based on the clinical correlation with histopathological findings (pauci-inflammatory subepidermal cleavage or with a neutrophilic infiltrate) and the demonstration of the presence of anti-collagen VII IgG in situ by direct immunofluorescence, or circulating anti-collagen VII IgG through indirect immunofluorescence and/or ELISA. There is no specific therapy for epidermolysis bullosa acquisita and the response to treatment is variable, usually with complete remission in children and a worse prognosis in adults with mucosal involvement. Systemic corticosteroids and immunomodulators (colchicine and dapsone) are alternatives for the treatment of mild forms of the disease, while severe forms require the use of corticosteroid therapy associated with immunosuppressants, intravenous immunoglobulin, and rituximab.
Topics: Adult; Autoantibodies; Autoimmune Diseases; Blister; Child; Epidermolysis Bullosa Acquisita; Humans; Immunoglobulins, Intravenous; Pemphigoid, Bullous
PubMed: 35701269
DOI: 10.1016/j.abd.2021.09.010 -
Giornale Italiano Di Dermatologia E... Dec 2020Acne fulminans (AF) is a rare and severe form of inflammatory acne presenting clinically with an abrupt outburst of painful, hemorrhagic pustules and ulceration, that... (Review)
Review
Acne fulminans (AF) is a rare and severe form of inflammatory acne presenting clinically with an abrupt outburst of painful, hemorrhagic pustules and ulceration, that may or may not be associated with systemic symptoms, such as fever, polyarthritis, and laboratory abnormalities. It typically affects male teenagers with a pre-existing acne. Although the pathogenetic mechanism has not been established yet, a role of genetic, abnormal immunologic response, drugs intake, hormonal imbalance and viral infection, as causal factors, has been identified. AF may occur as a single disease or may be associated with other disorders. Traditionally, AF has been classified, on the basis of the presence of systemic involvement, in "acne fulminans" and acne fulminans "sine fulminans," when no systemic involvement is present. Recently, four clinical variants have been proposed: acne fulminans with systemic symptoms (AF-SS), acne fulminans without systemic symptoms (AF-WOSS), isotretinoin-induced acne fulminans with systemic symptoms (IIAF-SS), isotretinoin-induced acne fulminans without systemic symptoms (IIAF-WOSS). The diagnosis of AF is usually based on clinical history and physical examination. No specific laboratory abnormalities are generally found. In selected cases, biopsy and/or radiologic imaging are helpful for a correct diagnosis. The treatment significantly differs from severe acne according to severity of clinical presentation and possible systemic involvement. Currently, systemic corticosteroids (prednisolone) and retinoids (isotretinoin) represent the first choice of treatment. Dapsone, cyclosporine A, methotrexate, azathioprine, levamisole, and biological agents such as anakinra, infliximab, adalimumab may be considered as alternative therapies in selected cases. Adjunctive topical and physical therapies may also be considered.
Topics: Acne Vulgaris; Acquired Hyperostosis Syndrome; Adolescent; Adrenal Cortex Hormones; Adult; Androgens; Anti-Inflammatory Agents; Arthralgia; Combined Modality Therapy; Debridement; Dermatologic Agents; Diagnosis, Differential; Disease Progression; Female; Humans; Immunosuppressive Agents; Inflammation; Isotretinoin; Lasers, Dye; Low-Level Light Therapy; Male; Photochemotherapy; Propionibacteriaceae; Retinoids; Symptom Assessment; Young Adult
PubMed: 33084268
DOI: 10.23736/S0392-0488.20.06711-5 -
The Journal of Allergy and Clinical... May 2022Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is one example of a severe delayed T-cell-mediated adverse drug...
Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is one example of a severe delayed T-cell-mediated adverse drug reaction. DIHS/DRESS presents with fever, widespread rash and facial edema, organ involvement, and hematological abnormalities, including eosinophilia and atypical lymphocytosis. DIHS/DRESS is associated with relapse 2 to 4 weeks after acute symptoms, often coinciding with reactivation of prevalent chronic persistent human herpesviruses such as human herpesvirus 6, EBV, and cytomegalovirus. The mortality of DIHS/DRESS is up to 10% and often related to unrecognized myocarditis and cytomegalovirus complications, with longer-term consequences that contribute to morbidity including autoimmune diseases such as thyroiditis. It is essential that all potential drug causes, including all new drugs introduced within the 8 weeks preceding onset of DIHS/DRESS symptoms, are identified. All potential drug culprits, as well as drugs that are closely related structurally to the culprit drug, should be avoided in the future. Systemic corticosteroids have remained the mainstay for the treatment of DIHS/DRESS with internal organ involvement. Steroid-sparing agents, such as cyclosporine, mycophenolate mofetil, and monthly intravenous immune globulin, have been successfully used for treatment, and careful follow-up for cytomegalovirus reactivation is recommended. Strong associations between HLA class I alleles and DIHS/DRESS predisposition include HLA-B∗13:01 and dapsone, HLA-B∗58:01 and allopurinol, and HLA-B∗32:01 and vancomycin. These have opened a pathway for prevention, risk stratification, and earlier diagnosis. Single-cell sequencing and other studies of immunopathogenesis promise to identify targeted treatment approaches.
Topics: Cytomegalovirus; Drug Hypersensitivity Syndrome; Eosinophilia; Exanthema; Herpesvirus 6, Human; Humans
PubMed: 35176506
DOI: 10.1016/j.jaip.2022.02.004 -
Experimental and Therapeutic Medicine Oct 2020Ocular cicatricial pemphigoid is a particular form of mucous membrane pemphigoid and it is characterized by a chronic bilateral conjunctivitis with relapsing-remitting... (Review)
Review
Ocular cicatricial pemphigoid is a particular form of mucous membrane pemphigoid and it is characterized by a chronic bilateral conjunctivitis with relapsing-remitting periods. Without therapy 75% of the cases develop visual loss due to major ocular complications (e.g. severe dry-eye syndrome, corneal erosions, corneal keratinization, entropion, symblepharon). Pathogenesis remains uncertain and probably linked to an autoimmune type II hypersensitivity response in patients with a genetic predisposition and exposure to different environmental triggers. With a worldwide distribution, no racial predilection and an estimated incidence that largely varies from 1/10,000-1/60,000, ocular cicatricial pemphigoid predominantly affects women aged ~60 years. Conjunctival biopsy with direct immunofluorescence is the gold standard in diagnosis confirmation, but up to 40% of the patients have a negative biopsy result that does not rule out the diagnosis. The skin and many other mucous membranes (e.g. oral, trachea, esophagus, pharynx, larynx, urethra, vagina and anus) may be involved. The disease grading relies on Foster staging system (based on clinical signs) and Mondino and Brown system (based on the inferior fornix depth loss). The differential diagnosis includes atopy, allergies, trauma, chemical burns, radiation, neoplasia, infectious, inflammatory and autoimmune etiologies. The main goals of the treatment are to stop disease progression, to relieve symptoms and to prevent complications. With long-term systemic therapy 90% of the cases can be efficiently controlled. While Dapsone is the first-line treatment in mild to moderate disease in patients without G6PD deficiency, more severe cases require immunosuppressant therapy with azathioprine, mycophenolate mofetil, methotrexate or cyclosporine. Cyclophosphamide, biologics (etanercept or rituximab) and intravenous immunoglobulin therapy are usually reserved for recalcitrant disease and unsatisfactory results to conventional therapy. Dry eye syndrome requires constant lubricating medication and topical steroids, cyclosporine-A and tacrolimus. Surgery should be planed only in quiescent phase as minor conjunctival trauma can significantly worsen the disease.
PubMed: 32905166
DOI: 10.3892/etm.2020.8972 -
Journal of the European Academy of... Oct 2022Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and...
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life.
OBJECTIVES AND METHODOLOGY
The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence-based or rely on expert opinion. The degree of consent among all task force members was included.
RESULTS
Treatment depends on the severity of BP and patients' comorbidities. High-potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B-cell-depleting therapy and intravenous immunoglobulins may be considered in treatment-resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations.
CONCLUSIONS
The guidelines for the management of BP were updated. They summarize evidence- and expert-based recommendations useful in clinical practice.
Topics: Adrenal Cortex Hormones; Aged; Blister; Dermatology; Humans; Pemphigoid, Bullous; Quality of Life; Venereology
PubMed: 35766904
DOI: 10.1111/jdv.18220 -
American Journal of Clinical Dermatology May 2021Dermatitis herpetiformis (DH), presenting with an intense itch and blistering symmetrical rash, typically on the elbows, knees, and buttocks, is a cutaneous... (Review)
Review
Dermatitis herpetiformis (DH), presenting with an intense itch and blistering symmetrical rash, typically on the elbows, knees, and buttocks, is a cutaneous manifestation of celiac disease. Though overt gastrointestinal symptoms are rare, three-fourths of patients with DH have villous atrophy in the small bowel, and the rest have celiac-type inflammatory changes. DH affects mostly adults and slightly more males than females. The mean age at onset is about 50 years. DH diagnosis is confirmed by showing granular immunoglobulin A deposits in the papillary dermis. The DH autoantigen, transglutaminase 3, is deposited at the same site in tightly bound immune complexes. At present, the DH-to-celiac disease prevalence is 1:8. The incidence of DH is decreasing, whereas that of celiac disease is increasing, probably because of improved diagnostics. In DH, the treatment of choice for all patients is a gluten-free diet (GFD) in which uncontaminated oats are allowed. At onset, most patients need additional dapsone to rapidly control the rash and itching. Dapsone can be stopped after a mean of 2 years, and a strict lifelong GFD alone is required. Dietary adherence offers an excellent long-term prognosis for patients with DH, with a normal quality of life and all-cause mortality.
Topics: Adult; Age Factors; Celiac Disease; Combined Modality Therapy; Dapsone; Dermatitis Herpetiformis; Dermis; Diet, Gluten-Free; Female; Humans; Immunoglobulin A; Intestinal Mucosa; Intestine, Small; Male; Patient Compliance; Prevalence; Prognosis; Quality of Life; Risk Factors; Sex Factors; Treatment Outcome
PubMed: 33432477
DOI: 10.1007/s40257-020-00584-2 -
Dermatology and Therapy Aug 2023Chronic spontaneous urticaria (CSU) is a condition in which wheals, angioedema, and pruritus occur spontaneously and recurrently for at least 6 weeks. The etiology of... (Review)
Review
Chronic spontaneous urticaria (CSU) is a condition in which wheals, angioedema, and pruritus occur spontaneously and recurrently for at least 6 weeks. The etiology of this disease is partially dependent on production of autoantibodies that activate and recruit inflammatory cells. Although the wheals can resolve within 24 h, symptoms have a significant detrimental impact on the quality of life of these patients. Standard therapy for CSU includes second-generation antihistamines and omalizumab. However, many patients tend to be refractory to these therapies. Available treatments such as cyclosporine, dapsone, dupilumab, and tumor necrosis factor alpha (TNFa) inhibitors have been used with success in some cases. Furthermore, various biologics and other novel drugs have emerged as potential treatments for this condition, and many more are currently under investigation in randomized clinical trials.
PubMed: 37386330
DOI: 10.1007/s13555-023-00972-6 -
International Journal of Molecular... Oct 2022Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy,... (Meta-Analysis)
Meta-Analysis Review
Dapsone (DDS), Rifampicin (RIF) and Ofloxacin (OFL) are drugs recommended by the World Health Organization (WHO) for the treatment of leprosy. In the context of leprosy, resistance to these drugs occurs mainly due to mutations in the target genes (Folp1, RpoB and GyrA). It is important to monitor antimicrobial resistance in patients with leprosy. Therefore, we performed a meta-analysis of drug resistance in Mycobacterium leprae and the mutational profile of the target genes. In this paper, we limited the study period to May 2022 and searched PubMed, Web of Science (WOS), Scopus, and Embase databases for identified studies. Two independent reviewers extracted the study data. Mutation and drug-resistance rates were estimated in Stata 16.0. The results demonstrated that the drug-resistance rate was 10.18% (95% CI: 7.85-12.51). Subgroup analysis showed the highest resistance rate was in the Western Pacific region (17.05%, 95% CI:1.80 to 13.78), and it was higher after 2009 than before [(11.39%, 7.46-15.33) vs. 6.59% (3.66-9.53)]. We can conclude that the rate among new cases (7.25%, 95% CI: 4.65-9.84) was lower than the relapsed (14.26%, 95 CI%: 9.82-18.71). Mutation rates of Folp1, RpoB and GyrA were 4.40% (95% CI: 3.02-5.77), 3.66% (95% CI: 2.41-4.90) and 1.28% (95% CI: 0.87-1.71) respectively, while the rate for polygenes mutation was 1.73% (0.83-2.63). For further analysis, we used 368 drug-resistant strains as research subjects and found that codons (Ser, Pro, Ala) on RpoB, Folp1 and GyrA are the most common mutation sites in the determining region (DRDR). In addition, the most common substitution patterns of Folp1, RpoB, and GyrA are Pro→Leu, Ser→Leu, and Ala→Val. This study found that a higher proportion of patients has developed resistance to these drugs, and the rate has increased since 2009, which continue to pose a challenge to clinicians. In addition, the amino acid alterations in the sequence of the DRDR regions and the substitution patterns mentioned in the study also provide new ideas for clinical treatment options.
Topics: Humans; Rifampin; Dapsone; Leprostatic Agents; Ofloxacin; Drug Resistance, Bacterial; Mycobacterium leprae; Leprosy; Mutation; Amino Acids; Microbial Sensitivity Tests
PubMed: 36293307
DOI: 10.3390/ijms232012443