key: cord-0828295-clj6rsk8 authors: Karimi Alavije, Mohammad; Karbalaie Niya, Mohammad Hadi; Sadeghzadeh-Bazargan, Afsaneh; Nikkhah, Mehdi; Faraji, Amirhossein; Motamed, Nima; Safarnezhad Tameshkel, Fahimeh; Zamani, Farhad title: Cutaneous hemorrhagic bullae in a patient with COVID-19: A case report date: 2021-02-01 journal: Med J Islam Repub Iran DOI: 10.47176/mjiri.35.15 sha: 95cf3cd1c3985320179a9056e552c67428f26b57 doc_id: 828295 cord_uid: clj6rsk8 COVID-19 was first discovered in Wuhan, China, and has spread rapidly around the world. The most important manifestation of COVID-19 was ARDS-like lung injury at first, but the involvement of other organs, such as kidney, heart, liver, and skin, was gradually reported. It is important to report and share all atypical manifestations of this disease to help other physicians to gain more knowledge about this new viral disease. As mentioned, there are also studies that show different types of cutaneous involvement in these patients, but due to the lack of more detailed studies in this field, and on the other hand, the possible usefulness of skin lesions as a diagnostic or alarming sign in the COVID-19 era, in this study we report a COVID-19 patient with a large hemorrhagic blister similar to sepsis-induced skin lesion. Despite the lack of common symptoms of the disease, the lung scan of the patient was positive for COVID-19. The novel coronavirus, first identified in Wuhan, China, was named as COVID-19 by the World Health Organization on February 11, 2020 (1) . The clinical spectrum of COVID-19 ranges from asymptomatic to symptomatic forms with subclinical or severe respiratory failure that require special care and include systemic sepsis, septic shock, and various syndromes involved in the functioning of the body. Common clinical symptoms include fever, cough, shortness of breath, fatigue, normal or decreased leukocytes, and pneumonia seen on radiographs. Other less common symptoms include headache, sore throat, and rhinorrhea (2) . A small number of patients may experience nausea and diarrhea; and symptoms that are more alarming need special care immediately after onset, which include persistent chest pain or pressure, breathing problems, confusion and bruising of the lips or face, and ad-vanced conditions that lead to pneumonia (3). The symptoms of the disease are similar in some cases. However, studies have shown that patients sometimes present with completely different symptoms and even with the symptoms of other diseases (4), and the doctor accidentally notices an involvement in lungs in patients with COVID-19 (5, 6), Also, in this disease, early diagnosis of suspicious people and the patient makes it possible to prevent further spread of the disease by timely treatment and discontinuation of the transmission chain. A 68-year-old diabetic woman came to our center because of an asymptomatic ecchymotic patch that suddenly appeared on her lower left limb. Except for diabetes, the patient did not have any history of other underlying dis- 2 ease or medication. The patient's diabetes was controlled by the diet and the patient did not receive any medication for it. At the time of the first visit, our patient did not have any constitutional symptoms and her vital signs were stable. (blood pressure (BP): 90/60 mmHg; respiration rate (RR): 18 breathes per minute, pulse rate (PR): 78 beats per minute; body temperature: 36.7°c, and O 2 saturation: 97%). The dorsalis pedis and posterior tibial pulses were bilaterally palpable. Due to diabetes history, the patient admitted with a coagulopathic-thrombotic impression for more evaluations. During hospitalization, ecchymotic lesion progressed to hemorrhagic bullae with erythematous border without additional symptoms (Fig. 1) . The physician first requested a complete laboratory examination by blood sampling, arterial and venous Doppler ultrasound, CT scan of the lungs, and ECG every 48 hours. In the laboratory studies, white blood cells count Cr, CPK, were in the normal range, and the results for troponin and CRP and troponin were negative. Also, the results of the patient's 24-hour urine culture test and 24hour and 48-hour blood culture tests were negative for any bacteria. Doppler sonography reported atheromatous plaque in the right common femoral artery, but the arterial and venous flow of the left lower limb was normal. Differential diagnoses for this skin lesion were as follows: 1. Because of diabetes, necrotizing fasciitis must be considered. However, these patients often have a bad general condition with very severe pain at the site of the involvement, which is not very consistent with the findings of our patient. 2. Coagulation disorders are due to infections and sepsis, such as disseminated intravascular coagulation (DIC) and purpura fulminans (PF), but the sepsis workup of our patient was negative except for chest CT scan findings that will be mentioned later. 3. Drug-induced necrosis and vaso-occlusion, such as heparin and warfarin necrosis, but the drug history of our patient was negative. 4. Vasculitis and vasculopathy are due to other underlying conditions, such as rheumatologic disorders or uncommon infections. Chest CT scan showed typical bilateral peripheral ground-glass opacities that were more predominant in lower lobes. However, SARS-CoV-2 RT-PCR was negative at the beginning of illness, so COVID-19 diagnosis was based on chest CT imaging (Fig. 2) . The only symptom of the patient was fever (38.8 one day after hospitalization), anorexia, and nausea without anosmia. The patient was hospitalized 11 days and underwent a standard national treatment protocol (Lopinavir/ritonavi (Kaletra) + Chloroquine + Ribavirin). Additionally, ceftriaxone, linezolid, ReciGen, and Remicade were prescribed for the patient. During the hospitalization, the patient did not have any internal or visceral bleeding and involvement. Also, due to high blood glucose, the patient had diabetic diet, and her wound was washed, and she was dressed regularly and daily. Two weeks after the infection, the skin lesion was changed to a necrotic ulcer and was finally healed with minimal scarring. In this study, the patient was a 68-year-old woman who had no common symptoms of COVID-19 and had only fever, anorexia, and nausea. She was initially visited with coagulation disorder and extensive sepsis bleeding, and COVID-19 disease was diagnosed for her during the additional examinations through a lung scan. So far, there have been few reports of skin lesions resulted by COVID-19 worldwide and in Italy (7), which was one of the centers of the disease. In Recalcati et al study on COVID-19 patients, there were a number of patients with skin manifestations like erythematous rash, extensive urticaria, rashes such as chickenpox and sometimes pruritus after hospitalization. The lesions usually healed within a few days. Studies at Medical Center (UNMC) at the Department of Dermatology of University of Nebraska showed that the existence of the skin rashes in 0.2% to 1.2% of the 1099 patients with COVID-19 in the laboratory by January 29, 3 2020, was confirmed in China (8-10), some of which had skin lesions since the beginning of the disease and some others at the time of hospitalization. Estébanez et al (11) also examined skin lesions in these patients in the study of the clinical features of COVID-19 and studied a 28-yearold woman without the previous medical history who visited the hospital with symptoms of COVID-19. The patient had erythematous plaques in the heel area that had become more severe over time. Recently, vascular injury and thrombotic events, especially in critical COVID-19 patients, have been reported in some studies, some of these patients also had cutaneous manifestations. These studies proposed the hyperactive immunological responses and cytokine storm in the pathogenesis of COVID-19 (12, 13) . In the case we reported, the lesions were the same as the coagulation disorder manifestation and extensive sepsis sign, which may be produced due to immune responses to COVID-19 and a history of diabetes. In conclusion, due to the very low percentage of skin symptoms in patients and their neglect and because of possibility of diagnosing them as the skin diseases as well as the very high prevalence of the disease and the possible mutations in the virus leading to various symptoms in patients, more studies are needed, so that it can help physicians to have a more accurate diagnosis of the disease. 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Dermatol Ther Cutaneous manifestations and considerations in COVID-19 pandemic: A systematic review The authors declare that they have no competing interests.