Review of drugs used to treat COVID-19 which can cause hypersensitivity reactions!

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REVIEW OF DRUGS USED TO TREAT COVID-19 THAT CAUSE HYPERSENSITIVITY REACTIONS!

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REVIEW OF DRUGS USED TO TREAT COVID-19 THAT CAUSES HYPERSENSITIVITY REACTIONS Keywords: COVID-19, Pharmacy, Drugs, Adverse Reactions

The different candidate drugs that are used to treat COVID-19, can cause adverse effects such as hypersensitivity reactions, the drugs in this review are classified into four groups according to their potential roles in different stages of the disease such as:

Antiviral drugs Antiviral drugs and / or immunomodulatory drugs used in viral pneumonia Anti-cytokine and anti-inflammatory drugs considered during macrophage activation syndrome (MAS) and cytokine storm; anti-inflammatory drugs in ARDS Antiplatelet and anticoagulant drugs in coagulopathy

Acronym ACD: Acute contact dermatitis; AGEP: Acute generalized exanthematouspustulosis; BAT: Basophil activation n test; DIHR: Desensitization for immediate hypersensitivity reactions; DNIHR: Desensitization for non-immediate hypersensitivity reactions; DPT: Drug provocation test; DRESS: Drug related eosinophilia systemic symptoms; FDE: Fixed drug eruption; HIT: Heparin induced thrombocytopenia; IDT: Intradermal test; IHR: Immediate hypersensitivity reaction; Injection site reaction: ISR; Generalized delayed exanthema: GDE; LTT: Lymphocyte transformation test; MPE: Maculopapular eruption; NIHR: Nonimmediate hypersensitivity reaction; PT: Patch test; SJS: Stevens Johnson syndrome; SPT: Skin prick test; ST: Skin test; TEN: Toxic epidermal necrolysis;Urticaria: U

1. ANTI-VIRAL AGENTS USED FOR VIRAL PNEUMONIA Ribavirin: Ribavirin is used in combination with pegylated interferon α2a, however when used together it can cause cutaneous DHR. Ribavirin alone causes dermatitis, alopecia, and photoallergic eczematous reactions, and the risk of DHR increases when used in combination therapies: rash, dermatitis, and pruritus.

Lopinavir / ritonavir (LPV / r): It has been shown to cause generalized acute exanthematous pustulosis (AGEP) which was described in two cases receiving LPV / r. In 199 patients, only two have been found to experience self-limiting rashes. A recent study evaluating 217 patients from China revealed that most adverse drug reactions (ADRs) were associated with LPV / r and umifenovir with 63.8% and 18.1% respectively.

Darunavir: Can induce a variety of delayed skin rashes, from mild MPE in most cases, to severe blistering skin reactions in HIVinfected patients. Two patients receiving darunavir required cessation of treatment due to severe shock. Darunavir contains a fraction of sulfonamide and should be used with caution in patients with a known sulfonamide allergy.

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2. ANTIVIRAL AND / OR IMMUNOMODULATORY DRUGS USED FOR VIRAL PNEUMONIA Azithromycin: Urticaria is the most frequent manifestation; additionally, anaphylaxis may occur. With respect to NIHR, MPE is described to occur independently or only in the presence of a concurrent infection. Azithromycin has been implicated in contact dermatitis in both occupational and non-occupational settings. Cases of Fixed Drug Eruption (FDE), AGEP, and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), SJS, Leukocytoclastic Vasculitis, and Hypersensitivity Myocarditis were reported.

Hydroxychloroquine / Chloroquine: Dermatological ADR is difficult to distinguish as a side effect or an allergic reaction to these medications or an outbreak of the underlying dermatological disease. The most common manifestation is mild itchy MPE within the first 4 weeks of treatment. High association with AGEP, DRESS cases such as pustular DRESS, erythema multiforme, bullous erythema, SJS / TEN and photoallergic dermatitis. Professional contact dermatitis has also been reported.

Ivermectin: Causes hypersensitive reactions, according to different rare case reports of multiple FDE, DRESS confirmed by skin biopsy and blood eosinophilia, confirmed SJS and TEN by skin biopsy were published.

3. ANTI-CYTOKINE / ANTI-INFLAMMATORY DRUGS USED FOR MAS / CYTOKINE STORM / ARDS Anakinra: Can cause RAM in 75% of patients. Many of them are related to reactions at the injection site, within the first weeks of application and can present as IHR or NIHR, in IHR as urticaria, angioedema, anaphylaxis and NIHR as infiltrators. Erythematous skin plaques were rarely reported as single cases. IHR After a first dose of anakinra was reported in one case possibly due to components that can induce direct mast cell degranulation.

Cyclosporine: Rare cases of pruritus, urticaria, angioedema, and anaphylaxis have been reported. The possible mechanisms may be both immunological and non-immunological, which seems to depend on the route of administration and formulation.

Colchicine: Rare cases of anaphylaxis, FDE confirmed with DPT. For PT, it is recommended to dilute colchicine 1% in petrolatum.

Glucocorticoids: RSIs are generally rare and mostly IgE-mediated. In a literature review from 2004-2014, anaphylaxis was the most common manifestation reported followed by urticaria and / or angioedema. Methylprednisolone was involved in 41% of reactions, followed by prednisolone (20%), triamcinolone (14%) and hydrocortisone (10%).

4. ANTI-COAGULANT AND ANTI-AGGREGANT DRUGS USED FOR COAGULOPATHY

Heparin and low molecular weight heparins (LMWHs): UFH can induce all kinds of DHR, mostly type IV and type II. NIHR cutaneous to subcutaneous heparin occurs at the injection site as itchy erythematous or eczematous plaques usually on the 7th -10th day of treatment; although they can appear on day 1-3 in case of antecedent sensitization. NIHR risk factors for heparin are obesity, female gender, age, pregnancy. If treatment continues regardless of a local reaction, the patient may develop generalized eczema or rash.

Dipyridamole: DHRs related to dipyridamole are extremely rare. They can cause late eczematosis in adult patients. Anaphylaxis or anaphylaxis as reactions were described in two cases, however, they lack diagnostic tests.

Conclusions: This review contains information on different medications that are candidates for treatment to treat COVID-19. At the moment there have not been many studies and case reports, and there are very few publications that can help to correlate the information that is currently obtained. Despite the small amount of information that has been obtained, it is clear that most of these reactions are rare. However the risk of DHR reactions should not be neglected.

More clinical trials regarding reports of DHR is required in order to obtain a greater amount of data and records.

All credits of scientific information are for the authors of the scientific article creation!

Scientific information reference: Gelincik, A., Brockow, K., Çelik, G. E., Doña, I., Mayorga, L., Romano, A., … Torres, M. J. (2020). Diagnosis and management of the drug hypersensitivity reactions in Coronavirus disease 19. Allergy.

Link: sci-hub.tw/10.1111/all.14439

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