key: cord-0849626-tcjjdp37
authors: Miladi, Ronak; Janbakhsh, Alireza; Babazadeh, Arefeh; Aryanian, Zeinab; Ebrahimpour, Soheil; Barary, Mohammad; Sio, Terence T.; Wollina, Uwe; Goldust, Mohamad; Mohseni Afshar, Zeinab
title: Pustular psoriasis flare‐up in a patient with COVID‐19
date: 2021-10-07
journal: J Cosmet Dermatol
DOI: 10.1111/jocd.14508
sha: 6181b08193ca4cf652f4b0b798fb27d9a42fb485
doc_id: 849626
cord_uid: tcjjdp37

INTRODUCTION: The various cutaneous manifestations have lately appeared in the setting of COVID‐19. Psoriasis flare‐ups have been reported during a COVID‐19 infection. CASE PRESENTATION: We present a case of a 32‐year‐old woman with COVID‐19 who presented with generalized pustular psoriasis. She received oral prednisolone, hydroxyzine, and topical clobetasol. The patient received follow‐up two weeks later and found that her lesions were favorably desquamating. METHODS: The PubMed, SCOPUS, and ISI Web of Science databases were thoroughly searched for English studies reporting psoriasis flare‐ups following SARS‐CoV‐2 infection. Ten case reports/series were included after screening. CONCLUSIONS: Our case report brings awareness to clinicians for the possible cutaneous manifestation of COVID‐19, which should be considered part of the differential diagnoses.

| 3365 MILADI et AL. of the nasopharyngeal swab tested for SARS-CoV-2 was positive, and the lung computed tomography (CT) scan was indicative of COVID-19. Although drug eruption, especially acute generalized exanthematous pustulosis (AGEP), was the most probable diagnosis, due to constitutional symptoms and elevated inflammatory markers, rheumatologic and immunologic disorders were also suspected regarding her age. Therefore, comprehensive diagnostic workup, including antinuclear (ANA), anti-double-stranded DNA (anti-dsDNA), anti-Smith (anti-Sm), anti-ribonuclear protein (anti-RNP), and anti-Ro/La, anti-histone (AHAs) antibodies, and HLA-B27 were performed, with all were negative.

Acute retroviral syndrome and serum sickness were also among the differential diagnoses, which were ruled out by negative test results of hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency viruses (HIV). According to the consultant dermatologist, oral prednisolone 50 mg daily, cyclosporine 200 mg daily in divided doses, topical clobetasol 0.05% were started for the patient, and a skin biopsy was suggested. Histologic examination demonstrated skin tissue with intermittent parakeratosis and exaggerated spongiform pustules of Kogoj and sub-corneal micro-abscesses of Munro, epidermis with mild acanthosis, and neutrophilic exocytosis.

Moreover, the upper dermis showed perivascular lymphocytes and neutrophils whiteout eosinophils, which were compatible with pustular psoriasis. The patient was then recommended to be followed up as an outpatient. At her 2-week follow-up, her lesions began to desquamate, and she was in a more favorable condition toward healing at this time.

Psoriasis is a cutaneous disorder triggered by various factors, such as medications and infections. Table 1 summarized previous reported cases of psoriasis associated with COVID-19. This pandemic can increase the psoriasis cases by limiting patients' access to required healthcare settings in many countries, 9 increasing the emotional stress in patients, which itself could act as a catalyst for the onset and aggravation of psoriasis. 10, 11 Thus, maximizing the psychosocial support available to patients with this condition during the current pandemic may significantly influence the disease activity. 12 Moreover, SARS-CoV-2 infection causes a hyperinflammatory response in patients, often known as COVID-19 cytokine storm syndrome (COVID-CSS). 13 Thus, a surge in the secretion of pro-inflammatory cytokines, such as tumor necrosis factorα (TNFα), interleukin-1α/β (IL-1α/β), 13 and IL-17, 14 which are all upregulated in the COVID-CSS, can be another pathophysiology of psoriasis in these patients. 12, 15 Another important etiology of this condition in COVID-19 patients is believed to be mediated via COVID-19-related medications. 12 Antimalarial agents were the most widely used drugs in COVID-19 treatment early in the pandemic. The cutaneous side effects of such drugs, such as HCQ, include skin eruptions such as xerosis, generalized pustulosis, hives, and most important of all, psoriasis exacerbation. 16 The exacerbation of psoriasis by chloroquine (CQ) occurs more frequently than HCQ. Other factors responsible for this complication include drug dosage, duration, and underlying photosensitivity conditions. Sometimes, cutaneous involvements are not typical for psoriasis. Therefore, they may be mentioned as psoriasiform. The difference is the less erythema and scaling of psoriasiform lesions and sparing of knees and elbows than true psoriasis. 17 HCQ is also a well-known triggering factor in psoriasis flare-ups. The underlying mechanism contributing to this condition is the inhibitory effect of HCQ on epidermal trans-glutaminase, leading to the epidermal cells collection and its promotion effects on interleukin-17 (IL- 17) production resulting in the overgrowth of keratinocytes. 18 In addition, some studies reported that the median period between newly consumed HCQ and the first appearance of an eruption is 1-2 weeks. 21 Thus, the appearance of rashes at least one month after discontinuation of HCQ in the current case is rare. It is important to note, due to suspicion of psoriasis, its type should be considered, such as a drug-induced pustular type, Von Zumbusch type of generalized pustular psoriasis (GPP), the idiopathic annular type, and HCQ-induced type. The vital issue is that usually, a pustular drug eruption subsides spontaneously or responds to corticosteroids. Our patient did partially respond to this first-line therapy, but eruptions reappeared immediately after treatment cessation.

Because of the relatively long period between drug consumption and skin eruption onset, pustular psoriasis induced by HCQ seems unlikely. The von Zumbusch type of generalized pustular psoriasis manifests by extensive pustules on erythematous skin, leading to diffuse scaling after rupture. 22 It is usually accompanied by fever and burning feeling, and if septicemia occurs, it may result in death.

Therefore, the von Zumbusch type of generalized pustular psoriasis or the idiopathic annular type might have happened. Besides, in any psoriasis-like lesion, subacute cutaneous lupus erythematosus (SCLE) is yet a significant impression. The primary diagnostic markers for this disorder are Anti-Ro ⁄SSA antibodies, both of which were negative in our patient.

In adults, first-line treatment options for pustular psoriasis include systemic retinoids (acitretin), cyclosporine, and methotrexate.

Although retinoids have the highest efficacy among the first-line treatment options, they have a high-risk potential for severe teratogenic effects that may last up to 3 years. 23 Hence, they are not good options in women of childbearing ages except in life-threatening situations. On the contrary, cyclosporine is a highly effective treatment for the severe manifestations of psoriasis with a relatively quick onset of action with improvement observed as early as 2 weeks from the initiation of treatment. 24 As there was some earlier evidence available in the literature about the effect of cyclosporine on coronaviruses replication in vitro, we hypothesize that the patient may benefit from its antiviral effects. Also, she will probably be at a lower risk of developing severe symptoms related to COVID-19.

On the other hand, methotrexate has a slower onset of action and potential hepatotoxicity and hematologic toxicity. 25 Thus, our recommendation is concomitant use of cyclosporine with prednisolone, but the patient did not continue therapy in the hospital. 

All authors declare no conflict of interest. 

As required by the Kermanshah University of Medical Sciences ethics committee, an informed consent form was taken from the patient to report the case.

Data sharing is not applicable to this article as no new data were created or analyzed in this study. 

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