Angina Bullosa Hemorrhagica in Five Covid-19-Positive Patients: A Concomitance or an Important Oral Manifestation

India was dreadfully affected by the second wave of COVID-19 pandemic in 2021 and several different oral lesions were observed in these patients. The most common oral manifestation observed was oral candidiasis on tongue. Other lesions reported were herpetic lesions, atypical ulcers and few angina bullosa like lesions.[1] Angina bullosa hemorrhagica (ABH) is an uncommon disorder appearing as hematic blisters in the oral and oropharyngeal region. The etiopathogenesis of this lesion is yet unknown and considered multifactorial. However, local trauma of the oral mucosa is the most commonly cited etiology in literature. Most common site of this lesion is the palate; however, it is also seen on labial mucosa, buccal mucosa, and tongue.[23] ABH occurring in patients with diabetes mellitus and hypertension has already been described in literature.[23] Our article describes this enigmatic lesion in five COVID-19 patients. To the best of our knowledge, they are amongst the first ever reported cases in Indian Literature. As oral medicine specialists, we have diagnosed several oral manifestations in COVID-19-positive patients during their stage of active infection in the year 2021. During this period, we came across five cases of ABH. All the 5 patients were positive for COVID-19, were home isolated, and were on medications. All patients were in the age group of 45 to 60 years. Three were on steroid inhalers along with azithromycin, paracetamol, anticoagulants, and zinc containing multivitamins while remaining 2 were on oral steroid therapy along with other previously mentioned drugs. All the patients were stressed due to their active disease. Three of them gave medical history of hypertension and diabetes while remaining 2 had no comorbidities. In all 5 patients, lesions presented as asymptomatic, single blood-filled bullae measuring 1 to 2 cm in diameter. Three lesions were on buccal mucosa [Figures 1 and 2], one on palate and one on labial mucosa [Table 1, Figure 3]. Hematological and coagulation investigations varied as per the stage of COVID-19 infection. Three patients had a recent drop in platelet count while 2 had neutrophilia [Table 1]. Classical clinical features lead to the diagnosis of ABH in all the 5 patients. All lesions ruptured spontaneously and healed within 5 days without scarring.Figure 1: A painless raised, round, dark red-colored blood-filled blister present on the left buccal mucosa measuring around 1 cm in diameterFigure 2: A large, painless, raised, bluish red-colored, blood-filled blister present on the right buccal mucosaTable 1: Showing details of all 5 patients including their coagulation profiles and duration of use of anticoagulants during active diseaseFigure 3: A raised, round, dark red-colored blood-filled blister with irregular surface on lower labial mucosaIt has been observed that there are several pathological reasons for the occurrence of ABH including minor trauma from any sharp foreign object, systemic diseases like diabetes, hypertension, vascular diseases or autoimmune conditions and inhaled corticosteroids use.[245] Blood dyscrasias have also been suggested as one of its causes due to various drugs administration.[35] It presents with sudden onset and appearance of bullae-like lesions filled with blood and ruptures spontaneously and heals mostly without any scars. Patients with COVID-19 show blood dyscrasias in hematological profile and anticoagulants are being prescribed in these patients as a treatment regimen. This may be one of the causes of ABH in these patients. Also, a huge downturn in immunity of an individual in this viral infection is housing various unexpected diseases. Chronic administration of inhaled, enteral or parenteral form of steroids for COVID-19 may be reducing the mortality due to the novel coronavirus but at the same time inviting various other diseases and conditions, one of which is ABH. The use of inhaled steroids is known to possibly affect collagen synthesis, causing atrophy of the mucous epithelium. As a result, the poor support provided by blood vessels present in the region could explain the development of ABH even in response to minor traumatic event.[4] Another etiological hypothesis of ABH in COVID-19 patients could be attributed to stress and anxiety. Many of these patients are already suffering with other comorbidities and increased stress can easily result in fragile mucosa leading to occurrence of these blood-filled blisters or ABH due to minor trauma caused during sample collection, intubations, and instrumentation during hospitalization. Also, such hemorrhagic blisters can be associated with thrombocytopenia associated with COVID-19 or due to the administration of anticoagulants. Most of the general practitioners are unaware of this lesion leading to misdiagnosis and patient is subjected to unnecessary treatment. As this condition spontaneously ruptures and heals without any treatment, we strongly recommend that ABH should be considered as one of the important oral manifestations in COVID-19 patients as these 5 cases were reported by us in a short span of 9 days during second wave of COVID-19 and several COVID-19-associated factors may predispose to its occurrence. In future, further observational studies should be conducted on large sample size to prove its occurrence in these patients. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.