key: cord-0913429-vyikj2m9 authors: Alberelli, M.C.; Panariello, A.; Olivi, M.; Borghi, A.; Zedde, P.; Corazza, M. title: Ulcus vulvae acutum and SARS‐CoV‐2: an aetiological role? date: 2021-07-21 journal: J Eur Acad Dermatol Venereol DOI: 10.1111/jdv.17463 sha: 5278c6bfdf2f1d55e4fe2c77643d70c9da63e615 doc_id: 913429 cord_uid: vyikj2m9 A 10-year-old girl presented with a sudden onset of fever and vulvar pain. Genital examination revealed vulvar edema especially affecting the labia minora; on the inner face deeply penetrating ulcers were observed bilaterally, a larger one of about 3 cm in diameter on the left and two on the right of about 2 cm in diameter (kissing ulcers). They were well-circumscribed, centrally covered with a fibrinous membrane and with purple edges (Figure 1). penetrating ulcers were observed bilaterally, a larger one of about 3 cm in diameter on the left and two on the right of about 2 cm in diameter (kissing ulcers). They were well-circumscribed, centrally covered with a fibrinous membrane and with purple edges (Fig. 1) . A clinical diagnosis of ulcus vulvae acutum was made. The patient had never had sexual intercourse, was not affected by any disease and was not taking drugs. Complete blood count was normal; laboratory findings showed elevated levels of serum C-reactive protein. Serology was negative for a wide spectrum of infectious diseases, namely syphilis, HSV 1-2, parvovirus B19, adenovirus and HIV; EBV serology and CMV serology was positive only for IgG. Bacterial cultures were negative including Mycoplasma and Trichomonas Vaginalis. Severe acute respiratory syndrome coronavirus 2 SARS-CoV-2) serology was requested; anti-SARS-CoV-2 IgM was positive with IgG antibodies negative. A molecular nasopharyngeal swab for the virus was performed with a negative result. Due to the severity of the clinical picture and for preventing bacterial superinfection, the patient was treated with topical and systemic antibiotics before the laboratory results became available. We empirically chose broad-spectrum molecules, i.e. gentamicin cream and oral amoxicillin. Because of the pain, she took ibuprofen for a total of 7 days. Healing appeared within 2 weeks with scarring. One month after healing, anti-SARS-CoV-2 IgG antibodies turned positive. Ulcus vulvae acutum was first described by Lipschutz in 1913 and was therefore also called ulcus vulvae acutum Lipschutz (UVAL). It is an uncommon clinical entity characterized by sudden painful vulvar ulcerations, of non-venereal origin, occurring mostly in young and virgin girls. Ulceration is often preceded by flu-like symptoms like fever, fatigue, malaise or chills. 1 Guidelines for diagnosis and therapy are lacking. A recently published systematic review of the literature, based on comparative and meta-analyses of the case reports described so far, proposes a diagnostic algorithm for a standardized diagnosis of UVAL (Table 1 ). 2 Our case fulfilled these diagnostic criteria. The aetiopathogenesis of UVAL is still unclear. Several infective agents have been associated with the disease in particular EBV, CMV, mycoplasma pneumoniae, flu virus, toxoplasmosis, mumps, salmonella and PVB19. 2 A hyperactivity of the immune system elicited by these infectious agents has been hypothesized as well as a type-III hypersensitivity reaction with vascular immune complex deposition, complement activation, micro-thrombosis and subsequent tissue necrosis. 3 In our patient, the initial flu-like symptoms and the current epidemiological situation made it mandatory to perform the serology for SARS-CoV-2. During coronavirus disease 2019 (COVID-19), numerous and polymorphous skin and, to a lesser extent, mucosal manifestations have been described with different degrees of severity. Sometimes, they can be observed in asymptomatic patients or in patients with very mild systemic symptoms of COVID-19, assuming therefore an important diagnostic value. 4 Some very severe cutaneous signs of COVID 19 are attributable to an immune disreactivity triggered by the virus with complement activation and possible interaction with coagulation pathways. 5 It is worthy of note that immune alteration and vascular damage are shared pathomechanisms for both UVAL-and COVID-19-associated skin manifestations. The necrosis and peripheral purpuric appearance of vulvar ulcers could also recall one of the typical skin patterns described during COVID-19. 6 The lack of definitive knowledge on the aetiology of UVAL, as well as the limited use of histology in confirming the imputability of a specific infectious agent, does not allow us to affirm with certainty that SARS-CoV-2 is the cause of UVAL in our patient. However, the timing of onset and the unique positive serology for SARS-CoV-2 may suggest an aetiological role of this virus. During the COVID-19 pandemic, it seems advisable to include SARS-CoV-2 as a possible cause of UVAL and to focus attention on the possible association with UVAL and its rare male counterpart, the juvenile gangrenous vasculitis of the scrotum. Dear Editor, Pemphigus vulgaris (PV) is a rare and severe autoimmune disorder of skin and mucosa. In PV, the production of autoantibodies against desmosomal proteins of the skin, namely desmoglein (Dsg) 1 and Dsg3, leads to a clinical phenotype characterized by blistering and severe erosions. Several factors including genetic susceptibility, certain drugs and malignant disorders have been reported to trigger or exacerbate PV. 1 Here, we report the first case of a patient, who developed PV following COVID-19 vaccination with the mRNA vaccine BNT162b2 (Comirnatyâ, Biontech/Pfizer). A 40-year-old female patient of Asian ethnicity was referred to our department following the outbreak of painful, non-healing erosions of the oral mucosa, the trunk and the back (Fig. 1a-c) . The patient's history revealed that first oral lesions occurred mid-January 5 days after the first administration of BNT162b2. Three days after the patient received the second vaccine dose, oral lesions worsened heavily; in addition, blisters and erosions occurred on the upper part of the body. Prior to vaccination, the patient was otherwise healthy, without any history of skin disease and without any medication. Due to the clinical presentation suspicious for pemphigus disease, we performed skin and blood sampling. The histology of lesional skin showed acantholysis within the lower epidermal layers, and the presence of a dense lymphocytic dermal infiltrate, accompanied by a rich presence of plasma cells (Fig. 1d) . Direct immunofluorescence from perilesional skin revealed a prominent deposition of IgG in a honeycomb-like intercellular epidermal pattern (Fig. 1e) . Finally, we detected high titres of autoantibodies against Dsg3 and Dsg1 in the patient's sera (974 and 124 RE/mL, respectively) (Euroimmun, L€ ubeck, Germany). With these findings, we confirmed the clinically suspected diagnosis of PV and initiated an immunosuppressive treatment with oral prednisone (1mg per kg body weight, eventually tapered) and azathioprine (100mg/day). 2 This approach ceased blistering and diminished autoantibody production. The patient is currently under regular clinical follow-ups in our clinic. Single cases of manifestation of PV following vaccination have been reported after administration of vaccines against rabies, influenza, hepatitis B, diphtheria, typhoid, tetanus and anthrax ( Table 1 ). The BNT162b2 vaccine is a lipid nanoparticle-formulated nucleoside-modified RNA (modRNA) encoding the SARS-CoV-2 full-length spike protein in its perfusion conformation. Following injection, common side effects like local redness, Lipschutz ulcers: evaluation and management of acute genital ulcers in women Ulcus vulvae acutum Lipsch€ utz: a systematic literature review and a diagnostic and therapeutic algorithm Genital ulcers associated with Epstein-Barr virus infection (ulcus vulvae acutum) Eruptions and related clinical course among 296 hospitalized adults with confirmed COVID-19 Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases COVID-19 and the Skin Development of severe pemphigus vulgaris following SARS-CoV-2 vaccination with BNT162b2 The patients presented in this paper have given written informed consent to the publication of their case details. None. Giovanni Damiani: Conceptualization, Data curation, Formal analysis, Investigation, Project administration, Visualization, Writingoriginal draft, Writingreview and editing. Alessia Pacifico: Investigation, Methodology, Project administration, Software, Validation. Writingreview and editing. Francesco Pelloni: Investigation, Project administration, Validation, Writingreview and editing. Matilde Iorizzo: Conceptualization, Methodology, Project administration, Resources, Supervision, Writingreview and editing.