Autoimmune bullous dermatoses associated with COVID-19 outbreak in Russian patients: a single case series.

Conflict of interest

The authors have no conflict of interest to declare.

Funding sources

None declared.

Editor

Autoimmune bullous diseases (AIBDs) are life‐threatening disorders resulting in either intraepidermal or subepidermal blisters requiring long‐term immunosuppressive therapies. Coronavirus disease 2019 (COVID‐19) is an infectious disease caused by severe acute respiratory syndrome (SARS) associated with SARS‐CoV‐2.

More than 3813 AIBD cases associated with COVID‐19 outbreak have been reported in the literature. ,

We observed nine patients aged ≥40 (mean: 57 years) with AIBDs during COVID‐19 pandemic. To assess AIBDs severity, we used PDAI and BPDAI scales. , To assess COVID‐19 severity, we used Brescia‐COVID Respiratory Severity Scale. PCR test for COVID‐19 was positive in all the patients. Four patients had mild, three moderate, and two severe COVID‐19 severity score (Table 1).

Table 1

Characteristic features of patients with AIBDs associated with COVID‐19 outbreak

Patient’s No.	Acronym	Age	Gender	Duration of AIBDs (years)	Supportive dose of CSs (mg/day)	Adjuvant therapy	Duration of supportive therapy (years)	AIBDs severity BPDAI/PDAI	AIBDs type	Concomitant disorders	SARS‐CoV‐2				Lethal outcome Yes/no
											AIBDs relapses during COVID‐19 outbreak		PCR test	Brescia‐COVID Respiratory Severity Scale
											Yes/no	Time of disseminated lesions onset
1	V	50	M	3	10	No	3	Mild	PV	No	No	NA	Positive	2	No
2	T	49	M	11	10	Azathioprine	11	Moderate	PV	No	No	NA	Positive	2	No
3	B	53	M	3	10	Azathioprine	2.5	Moderate	PV	Chronic gastritis	No	NA	Positive	1	No
4	D	77	F	13	10	Azathioprine	13	Severe	PF	Hypertension † Chronic gastritis	No	NA	Positive	3	Yes
5	T	40	M	1.5	NA	No	NA	Severe	PF	No	Yes	Third week from the AIBD debut	Positive	1	No
6	B	65	F	1	NA	Azathioprine	NA	Severe	PV	Hypertension † Paroxysmal supraventricular tachycardia	Yes	Third week from the AIBD debut	Positive	3	Yes
7	T	80	F	4	10	Azathioprine	2	Mild	BP	Hypertension †	No	NA	Positive	1	No
8	P	43	F	3	10	Azathioprine	3	Severe	PV	No	No	NA	Positive	2	No
9	L	60	F	3	8	No	3	Mild	PV	Diabetes mellitus	No	NA	Positive	1	No

NA, not applicable.

Hypertension stage 2, grade 2.

The diagnosis of AIBDs was confirmed histologically and immunohistochemically according to European guidelines (Fig. 1e, f). Three patients had a mild, two moderate (case #3; Fig. 1a, b, c, d) and four severe AIBDs. Six patients suffered from pemphigus vulgaris (PV), two had pemphigus foliaceus (PF) and one had bullous pemphigoid (BP). Five of nine patients had concomitant disorders: chronic gastritis, hypertension, paroxysmal supraventricular tachycardia and diabetes mellitus. The duration of AIBDs ranged from 1 to 13 years. There were no further AIBDs relapses in COVID‐19 patients (n = 7) who had ongoing systemic immunosuppressive therapy at the dose of 10 mg/day. Two of patients with severe COVID‐19 and without supportive systemic glucocorticoids (CS) developed severe AIBD and died (Table 1).

Figure 1

(a, b, c, d, e, f). Male patient (case #3, 53 years old) with PV: (a, b) before the treatment: erosions arising from the blisters affecting the oral mucosa; (c, d) after the treatment: regression of the erosions; (e) skin biopsy (H&E, original magnification ×200): suprabasilar blister with acantholysis, lymphohistiocytic infiltration in the upper dermis; (f) direct immunofluorescence microscopy: intercellular deposits of IgG.

Dermatological manifestations, such as AIBDs, identified in COVID‐19 patients in several countries. The hospitalisation rates and mortality because of COVID‐19 complications were 12.2 and 7.1 in BP and 7.5 and 1.5 in pemphigus patients per 1000 person‐years, respectively.

In a recent systematic review, Kasperkiewicz M et al. analysed 732 AIBDs cases. Those patients who received systemic immunomodulatory therapy were not at increased risk of severe COVID‐19 course. Considering the 1.5–3.6% mortality associated with COVID‐19 in the population, the mortality in elderly patients with AIBDs and comorbidities such as diabetes mellitus, hypertension and atrial fibrillation was 0.4%. Whereas, AIBDs patients with immunosuppressive therapy were not at increased risk of severe or fatal outcome. We examined nine COVID‐19 patients with previously diagnosed AIBDs and the mean age of 57 years (Table 1). Patients who did not receive immunosuppressive therapy during COVID‐19 outbreak had severe AIBDs debut and relapses with mortality corresponding to that in the literature.

Although old age and certain comorbidities, such as hypertension and diabetes, represent a well‐described risk factors for complicated COVID‐19, the role of immunosuppression remains controversial. Analysis suggests that patients with AIBDs receiving immunomodulatory therapies are basically not at increased risk of severe or fatal COVID‐19. According to Kridin K et al. 2021, BP patients had higher COVID‐19‐associated mortality. However, authors showed that maintaining CS and immunosuppressive adjuvant agents during the pandemic in AIBDs patients was associated with favourable outcomes.

There is a limited information concerning the impact of SARS‐CoV‐2 on the AIBDs course. AIBDs relapses during COVID‐19 pandemic could be associated with IFN‐1‐mediated activation of CD4+ and CD8+ cytotoxic T‐lymphocytes and proinflammatory cytokines release. Patients with AIBDs who received a maintenance dose of CS (10 mg/day) over 3 years showed no AIBDs relapses, whereas those without systemic CS therapy developed severe AIBDs during COVID‐19 outbreak. These two patients also had a severe COVID‐19 course. However, no clear and comprehensive data have been provided on the management of ongoing immunosuppressive therapies in these patients. To avoid mismanagement patients with AIBDs, they should be monitored regularly for symptoms of COVID‐19. Unjustified withdrawal of CS can cause AIBDs exacerbation, especially in severe disease.