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Year : 2022  |  Volume : 11  |  Issue : 4  |  Page : 373-376

COVID-19 and bullous pemphigoid: Coincidence or a true association?

1 Department of DVL, Gayatri Vidya Parishad Institute of Health Care and Medical Technology, Visakhapatnam, Andhra Pradesh, India
2 Consultant Pulmonologist, Gayatri Nursing Home, Vijaya Diagnostics Centre, Visakhapatnam, Andhra Pradesh, India
3 Consultant Pathologist, Vijaya Diagnostics Centre, Visakhapatnam, Andhra Pradesh, India

Date of Submission29-Oct-2021
Date of Decision23-Nov-2021
Date of Acceptance03-Dec-2021
Date of Web Publication17-Mar-2023

Correspondence Address:
Dr. Prathyusha Yakkala
Department of DVL, Gayatri Vidya Parishad Institute of Health Care and Medical Technology, Visakhapatnam, Andhra Pradesh - 530 048
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jdrntruhs.jdrntruhs_145_21

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Various dermatological manifestations have been reported in this pandemic of COVID-19. COVID and autoimmunity is known. We report a case of Bullous pemphigoid associated with COVID-19. Clinical features were suggestive of Bullous pemphigoid which was confirmed by histopathology, direct immunofluorescence and salt split technique. Patient did not respond to conventional therapy for BP. However, she responded dramatically to COVID-19 treatment with antiviral therapy. Though rare, this association between COVID and BP needs to be kept in mind while evaluating BP lesions during this pandemic.

Keywords: Autoimmunity, Bullous pemphigoid, COVID-19

How to cite this article:
Rao TN, Yakkala P, Tadikonda BR, Karri SB. COVID-19 and bullous pemphigoid: Coincidence or a true association?. J NTR Univ Health Sci 2022;11:373-6

How to cite this URL:
Rao TN, Yakkala P, Tadikonda BR, Karri SB. COVID-19 and bullous pemphigoid: Coincidence or a true association?. J NTR Univ Health Sci [serial online] 2022 [cited 2023 Mar 21];11:373-6. Available from: https://www.jdrntruhs.org/text.asp?2022/11/4/373/371751

  Introduction Top

The ongoing pandemic due to SARS-CoV-2 had been challenging to health care workers due to its varied presentations. COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Though the predominant symptoms are respiratory,[1] multiple cutaneous manifestations are reported.[2],[3] The six main clinical patterns[2] include urticarial rash, confluent erythematous/maculopapular/morbilliform rash, papulovesicular exanthem, chilblain-like acral pattern, livedo reticularis/racemosa-like pattern, purpuric “vasculitic” pattern. Others include the erythema multiforme-like eruption, pityriasis rosea-like rash,[4] multi-system inflammatory syndrome in children,[5] anagen effluvium.[6] Herein, we report a case of Bullous pemphigoid associated with COVID-19.

  Case Report Top

A 48-year-old female patient was admitted with severe itchy red lesions and fluid-filled lesions all over body for 5 days. The pruritus was so intense that she was having disturbed sleep and was irritable. She did not have a prior history of a similar disease. There was no history of any chronic disease or recent use of any medication. The lesions initially appeared on the trunk, limbs and rapidly progressed to involve the entire body in 2 days. On examination, the patient had low-grade fever (99 F) and other vitals were normal. She had multiple urticarial plaques, vesicles, bullae, and few erosions involving the entire body including palms and soles. The bullae were tense and not rupturing spontaneously [Figure 1]. There were no mucosal lesions. In view of tense bullae, urticarial plaques, and negative Nikolsky sign, a clinical diagnosis of Bullous pemphigoid was made. Biopsy was performed for histopathological examination and direct immunofluorescence testing. Injectable steroid (Methylprednisolone 40 mg once a day) was started under antibiotic cover along with antihistamines. However, she continued to progress and developed new lesions associated with intractable pruritus. Biopsy showed a subepidermal bulla with multiple eosinophils and neutrophils. Direct Immunofluorescence showed Ig G and C3 positivity at Dermo Epidermal junction confirming the diagnosis of Bullous Pemphigoid [Figure 2]. In view of progressive symptoms and signs, after 3 days, the patient was put on high dose IV Methylprednisolone 500 mg per day for 3 days. Still, the patient developed multiple new lesions and hence IV Immunoglobulin therapy at 0.5 gm/kg/day was initiated. Four days after starting IvIg, she developed a mild cough and continued to have mild fever. Her oxygen saturation at room air was 94%. As lesions were not remitting and in view of the prevailing COVID-19 pandemic, a COVID RT PCR test was performed which turned out to be positive. HRCT chest showed multiple confluent areas of ground-glass opacities with interstitial thickening in bilateral lungs, predominantly involving the lower lobes, suggestive of active viral pneumonitis and its sequelae––CO-RADS score 5 [Figure 3]. The CT severity score was 17/25. Inflammatory markers showed a significant raise in parameters (LDH, D dimer and CRP levels were 720 u/L, 2490 ng/ml and 84.2 mg/l respectively). The patient was immediately isolated and treatment for COVID-19 initiated as per protocol including Remdesivir 200 mg stat followed by 100 mg OD, Enoxaparin 60 mg OD, Dexamethasone 8 mg OD by pulmonologist. She improved clinically by marked reduction of pruritus and her Bullous pemphigoid lesions reduced significantly after 5 days of remdesivir therapy [Figure 4]. Patient is presently on 16 mg methylprednisolone without any new lesions for 2 weeks.
Figure 1: Clinical photo showing multiple tense bulla and vesicles, few erosions

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Figure 2: (a) Subepidermal blister (H and E 4x). (b) Blister shows mainly eosinophils (H and E 40x). (c) Linear pattern of C3 at DEJ (DIF 20x). (d) Salt split technique revealed mixed pattern (roof and floor) of C3 (DIF 40x)

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Figure 3: HRCT showing multiple confluent areas of ground glass opacities with interstitial thickening in bilateral lungs

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Figure 4: Post treatment photos showing complete healing of lesions

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  Discussion Top

This case highlights the rare possibility of viral diseases triggering bullous pemphigoid. The lesions regressed only after the concomitant viral infection was treated with remdesivir. After extensive search of literature, we could find only one similar case report[7] where patient in the third-week post-COVID infection developed a maculo-papular rash which was diagnosed as a viral exanthem, with small acral vesicular lesions. Two weeks later, she developed tense bullae. Biopsy and IF were suggestive of BP. The patient responded to oral Prednisolone and Doxycycline and subsequently tested negative for SARS-Cov2 in weeks 7 and 8. The authors[7] hypothesized that prolonged inflammation of the skin during the exanthem had left the damaged basement membrane susceptible to immune recognition by the host's immune system, thereby the development of autoantibodies to BP antigens, through antigenic mimicry of viral antigens. Contrastingly, our patient developed COVID and BP simultaneously.

Another possible explanation could be molecular mimicry between the virus and human proteins, where immune responses raised against COVID could cross react with human proteins which share peptide sequences with the virus.[8] Peptide sharing has been found between SARS-CoV-2 antigenic epitopes and different human proteins.[9] Sagi et al.[10] showed higher prevalence of antibodies to HBV, HCV, H. pylori, Toxoplasma gondii and CMV in patients with pemphigus and bullous pemphigoid. They suggested that infectious agents may play a role in inducing disease in a genetically susceptible host. Viruses especially herpes virus play a role in triggering Bullous pemphigoid.[11],[12] Similarly, COVID-19 can play a role in triggering autoimmune bullous diseases like Bullous pemphigoid.[8] Both BP and COVID-19 are prothrombotic states with an estimated 15-fold increased risk of venous thromboembolism in the acute phase. So prophylactic anticoagulation is suggested in this pandemic.[13]

Our case differs from idiopathic bullous pemphigoid in that lesions started concomitantly with COVID infection. The lesions did not respond to conventional treatment. Itching was intractable throughout, till remdesivir was administered. Lesions reduced only after initiation of anti-viral treatment. No new lesions appeared even after steroid tapering. We finally conclude that this rare association should be kept in mind during this COVID pandemic with extremely wide-ranging manifestations which have not yet been thoroughly studied.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Jeon J, Baruah G, Sarabadani S, Palanica A. Identification of risk factors and symptoms of COVID-19: Analysis of biomedical literature and social media data. J Med Internet Res 2020;22:e20509.  Back to cited text no. 1
Genovese G, Moltrasio C, Berti E, Marzano AV. Skin manifestations associated with COVID-19: Current knowledge and future perspectives. Dermatology 2021;237:1-12.  Back to cited text no. 2
Marzano AV, Cassano N, Genovese G, Moltrasio C, Vena GA. Cutaneous manifestations in patients with COVID-19: A preliminary review of an emerging issue. Br J Dermatol 2020;183:431-42.  Back to cited text no. 3
Ehsani AH, Nasimi M, Bigdelo Z. Pityriasis rosea as a cutaneous manifestation of COVID-19 infection. J Eur Acad Dermatol Venereol 2020;34:e436-7.  Back to cited text no. 4
Gupta A, Gill A, Sharma M, Garg M. Multi-system inflammatory syndrome in a child mimicking Kawasaki disease. J Trop Pediatr 2020;67:fmaa060.  Back to cited text no. 5
Shanshal M. COVID-19 related anagen effluvium. J Dermatol Treat 2020:1-2. doi: 10.1080/09546634.2020.1792400.  Back to cited text no. 6
Goon PKC, Bello O, Adamczyk LA, Chan JYH, Sudhoff H, Banfield CC. Covid-19 dermatoses: Acral vesicular pattern evolving into bullous pemphigoid. Skin Health Dis 2021;1:e6.  Back to cited text no. 7
Kasperkiewicz M. Covid-19, heat shock proteins, and autoimmune bullous diseases: A potential link deserving further attention. Cell Stress Chaperones 2021;26:1-2.  Back to cited text no. 8
Ehrenfeld M, Tincani A, Andreoli L, Cattalini M, Greenbaum A, Kanduc D, et al. Covid-19 and autoimmunity. Autoimmun Rev 2020;19:102597.  Back to cited text no. 9
Sagi L, Baum S, Agmon-Levin N, Sherer Y, Katz BS, Barzilai O, et al. Autoimmune bullous diseases the spectrum of infectious agent antibodies and review of the literature. Autoimmun Rev 2011;10:527-35.  Back to cited text no. 10
Patel F, Wilken R, Patel FB, Sultani H, Bustos I, Duong C, et al. Pathophysiology of autoimmune bullous diseases: Nature versus nurture. Indian J Dermatol 2017;62:262-7.  Back to cited text no. 11
  [Full text]  
Drago F, Nozza P, Casazza S, Brusati C, Bandelloni R, Rebora A. Human herpesviruses in bullous pemphigoid lesions. Br J Dermatol 2005;152:375-6.  Back to cited text no. 12
Drenovska K, Vassileva S, Tanev I, Joly P. Impact of COVID-19 on autoimmune blistering diseases. Clin Dermatol 2021;39:359-68.  Back to cited text no. 13


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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