Dear Editor, Growing evidence suggests that SARS‐CoV‐2 vaccination is associated with a variety of cutaneous reactions, also including autoimmune‐mediated conditions such as autoimmune blistering diseases such as bullous pemphigoid (BP). 1,2 We report new‐onset BP in two patients following the first SARS‐CoV‐2 vaccination.
There exist relatively sparse and conflicting data on high-level microsatellite instability (MSI-H) and deficient mismatch repair (dMMR) in cutaneous malignancies. We aimed to determine the expression profiles of MMR proteins (MSH2, MSH6, MLH1, and PMS2) in different progression stages of cutaneous squamous cell carcinoma (cSCC, 102 patients in total) by immunohistochemistry, and search for MSI-H in patients with low-level MMR or dMMR using multiplex-PCR. Low-level MMR protein expression was observed in five patients: One patient with primary cSCC < 2 mm thickness and low-level MLH1, three patients with primary cSCC > 6 mm (including one with low-level MSH2, as well as MSH6 expression, and two with low-level PMS2), and one patient with a cSCC metastasis showing low-level MSH2 as well as MSH6. Intergroup protein expression analysis revealed that MLH1 and MSH2 expression in actinic keratosis was significantly decreased when compared to Bowen’s disease, cSCC < 2 mm, cSCC > 6 mm, and cSCC metastasis. In cases with low-level MMR, we performed MSI-H tests revealing three cases with MSI-H and one with low-level MSI-L. We found low-level MMR expression in a small subset of patients with invasive or metastatic cSCC. Hence, loss of MMR expression may be associated with tumour progression in a small subgroup of patients with non-melanoma skin cancer.
Angioedema is a relatively rare but potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As with hereditary forms of angioedema (HAE), this adverse reaction is mediated by bradykinin. Research suggests that ACEi/ARB-induced angioedema has a multifactorial etiology. In addition, recent case reports suggest that some ACEi/ARB-induced angioedema patients may carry pathogenic HAE variants. The aim of the present study was to investigate the possible association between ACEi/ARB-induced angioedema and HAE genes via systematic molecular genetic screening in a large cohort of ACEi/ARB-induced angioedema cases. Targeted re-sequencing of five HAE-associated genes (SERPING1, F12, PLG, ANGPT1, and KNG1) was performed in 212 ACEi/ARB-induced angioedema patients recruited in Germany/Austria, Sweden, and Denmark, and in 352 controls from a German cohort. Among patients, none of the identified variants represented a known pathogenic variant for HAE. Moreover, no significant association with ACEi/ARB-induced angioedema was found for any of the identified common [minor allele frequency (MAF) >5%] or rare (MAF < 5%) variants. However, several non-significant trends suggestive of possible protective effects were observed. The lowest p-value for an individual variant was found in PLG (rs4252129, p.R523W, p = 0.057, p.adjust > 0.999, Fisher’s exact test). Variant p.R523W was found exclusively in controls and has previously been associated with decreased levels of plasminogen, a precursor of plasmin which is part of a pathway directly involved in bradykinin production. In addition, rare, potentially functional variants (MAF < 5%, Phred-scaled combined annotation dependent depletion score >10) showed a nominally significant enrichment in controls both: 1) across all five genes; and 2) in the F12 gene alone. However, these results did not withstand correction for multiple testing. In conclusion, our results suggest that HAE-associated mutations are, at best, a rare cause of ACEi/ARB-induced angioedema. Furthermore, we were unable to identify a significant association between ACEi/ARB-induced angioedema and other variants in the investigated genes. Further studies with larger sample sizes are warranted to draw more definite conclusions concerning variants with limited effect sizes, including protective variants.
Dear Editor, With the onset of the COVID-19 pandemic and the emergence of COVID-19 vaccinations, numerous cases of skin reactions related to SARS-CoV-2 infection and to vaccination have been reported, including urticaria, chilblain lesions and morbilliform rashes. 1,2 Furthermore, the induction or worsening of inflammatory skin diseases was observed. 3 However, reports on severe skin reactions like erythema exsudativum multiforme (EEM), Stevens-Johnson syndrome (SJS) and Fuchs syndrome (FS) related to SARS-CoV-2 infection are scarce. We here present a case of FS after SARS-CoV-2 infection.A 34-year-old Caucasian woman presented to our dermatological outpatient clinic with severe acute fatigue, fever, malaise, swelling of cervical lymph nodes and sudden development of infiltrating lesions on mucous membranes. Four days before, blisters and ulcers developed in the oral mucosa, the lips and the genital mucosae with concomitant conjunctivitis. No other skin lesions were observed. Initial treatment with acyclovir 5 × 800 mg by her general practitioner showed no improvement. The patient reported no other medical history, but an asymptomatic SARS-CoV-2 infection verified by an antigen test 2 weeks before first symptoms. Clinical examination revealed haemorrhagic erosions with crusting on the lips and eroded lingual lesions (Figure 1). Marked conjunctival infiltration was observed in both eyes (Figure 2). This symptom complex was clinically diagnosed as FS. To rule out differential diagnoses, extensive blood analyses were performed, and mucosal swabs taken, excluding herpes simplex virus (HSV) infection by polymerase chain reactions. Elevated C-reactive protein to 84 mg/L (reference: <5 mg/L) and thrombocytosis were observed (493 bn/L [150-370 bn/L]); liver and renal function test, white and red blood count, electrolytes and anti-streptolysin titre revealed normal results.The patient had been vaccinated against COVID three times, the last being applied 18 weeks before the onset of acute mucosal lesions. We thus concluded that this episode of FS was most likely triggered by SARS-CoV-2 infection. Due to malaise, fever, fatigue and severely worsening general condition, the patient was admitted to a dermatology hospital. Treatment included systemic prednisolone (100 mg/daily for 3 days), topical antiseptics and anaesthetic mouthwash. After ophthalmological review, prednisolone eye drops were applied for conjunctival involvement. The patient fully recovered within a week without any clinical sequelae.Clinical diagnosis of acute severe SJS-like mucosal lesions in the absence of extramucosal lesions has been described as FS. Currently, there is no published consensus on the specific criteria of FS. It is considered a rare clinical variant of erythema multiforme majus (EEM). 4 Although
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