key: cord-0820961-elxlxrb3
authors: Papanagnou, Dimitrios; Capobianco, Sara; Jean, Joseph
title: Hydroxychloroquine-Induced cutaneous reaction in treatment of COVID-19
date: 2021-02-02
journal: Vis J Emerg Med
DOI: 10.1016/j.visj.2021.100979
sha: 8accf08c4286615733c467d435ce6ceda01a700b
doc_id: 820961
cord_uid: elxlxrb3

nan

In the current era of the coronavirus disease 2019 pandemic , and the subsequent use of various novel drug therapies, including hydroxychloroquine, it is critical to maintain a high level of suspicion for adverse drug reactions for patients present to the emergency department (ED). As hydroxychloroquine continues to be utilized experimentally for COVID-19 across the world, this case highlights an important potential adverse reaction of the drug.

A 72-year-old Caucasian female with a past medical history of chronic obstructive pulmonary disease, type 2 diabetes mellitus, and a recent 2.5-week hospital admission for COVID-19, presented to the ED as a transfer from an outside hospital for a diffuse body rash that has been worsening for two days. She was discharged four days prior from a 2.5 week hospital admission for COVID-19. The patient did not endorse any known drug allergies besides codeine. During her recent hospital admission, she was treated with PO hydroxychloroquine (400 mg hospital day one, followed by 200 mg by mouth twice daily for a total of 8 doses). The last dose of hydroxychloroquine was 12 days prior to the development of the current rash symptoms. She was also given a 5-day course of intravenous ceftriaxone hospital days 4-9 (1 gram daily).

The patient was discharged from the hospital with a negative repeat COVID-19 test. She was started on home oxygen and metoprolol for new-onset atrial fibrillation. Two days later, she noticed a pruritic rash on her chest with accompanying dyspnea. The patient initially thought the rash was secondary to the cardiac monitor stickers placed during her hospital course, but her symptoms worsens in severity and spread to involve her abdomen, back, face, and extremities. She did not have any relief with diphenhydramine or over-the-counter topical steroids. She denied a history of a similar rashes in the past. She also denied intraoral, ocular, or genital involvement.

On physical examination, vital signs were within normal limits: temperature of 97.6 • F (36.4 • C), heart rate 97 beats/minute, respiratory rate 24 breaths/minute, blood pressure 128/52 mmHg, oxygen saturation 97% on 6 L nasal cannula. She appeared uncomfortable and slightly tachypneic, but in no acute respiratory distress. There were diffuse crackles in anterior and posterior lung fields bilaterally. On skin examination, there were diffuse pink to violaceous palpable papules coalescing into plaques over the face, trunk, extremities and back, covering approximately 85% body surface area (BSA). The rash appeared morbilliform centrally. There was no oral, ocular, or vaginal mucosal involvement. The rash spared the palms and soles. The papules were faintly blanchable in peripheral areas of involvement but not centrally. There was no evidence of any blister or vesicle formation and had a negative Nikolsky's sign.

Laboratory evaluation was significant for a neutrophilic leukocytosis with WBC 13.0 B/L (reference range 4.0 -11.0 B/L), neutrophils at 82.1% (reference range 40.0 -73.0%), as well as an elevated lactate level of 3.3 mmol/L (reference range 0.5 -2.0 mmol/L), and a CRP of 9.80 mg/dL (reference range ≤ 0.80 mg/dL). The patient also had a normal eosinophil count at 5.1% (reference range 0.0 -6.0%). Other notable normal results in the CMP: sodium at 137 mmol/L (reference range 135 -146 mmol/L), potassium at 4.1 mmol/L (reference range 3.3 -4.8 mmol/L), anion gap at 15 mg/dL (reference range 12 -27 mg/dL), creatinine at 0.92 mg/dL (reference range 0.70 -1.40 mg/dL), AST 26 IU/L (reference range 7 -35 IU/L), ALT 29 (reference range <30 IU/L).

The initial differential for this patient given the clinical history and examination findings included: Stevens Johnson Syndrome (SJS), Toxic epidermal necrolysis (TEN), Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and adverse drug reaction (ADR). DRESS and ADR were on the top of our differential.

DRESS is a well-documented serious consequence of various drugs, most commonly aromatic anticonvulsants, allopurinol, and sulfacontaining drugs. DRESS has an estimated mortality rate between 2 and 10%, rendering it an important diagnosis to maintain on the differential for patients with skin rash and fever in the emergency department. 1 DRESS consists of the clinical constellation of rash (most commonly morbilliform), fever, hematologic abnormalities (eosinophilia, atypical lymphocytosis), and multisystem organ involvement (most commonly liver, kidney, lung). 1 DRESS is also characterized by a latency of 2-8 weeks between drug exposure and onset of symptoms, 1 which fit this patient's clinical course. Although DRESS is a clinical diagnosis, the Registry of Severe Cutaneous Adverse Reactions (RegiS-CAR) Scoring system, is the most widely used scoring system to help confirm or exclude the diagnosis of DRESS. 1 Using the criterium outlined in RegiSCAR and the clinical history, examination and laboratory data, our patient did not meet the criteria for probable or definitive DRESS.

Hydroxychloroquine has the potential to cause a wide range of adverse reactions, including retinopathy, cardiomyopathy, hypoglycemia, neutropenia, neuromyopathy and various skin reactions. 2 Documented skin reactions from hydroxychloroquine range in severity from dermatitis to TEN. 2 Given the potential for hydroxychloroquine to cause skin reactions and the temporal relationship between the initiation of hydroxychloroquine and the patient's presentation, ADR was highly suspected. The Naranjo Adverse Drug Reaction Probability scale was created to help clinicians assess the likelihood that an ADR is occurring. 3 Using the Naranjo algorithm questionnaire, the patient had a calculated score of "5 ′′ , meaning the likelihood of an adverse drug reaction is "probable". 3 Our leading diagnosis given the clinical history, physical examination and laboratory studies, was an ADR secondary to hydroxychloroquine. DRESS was strongly considered, but at the patient's time of evaluation there was no evidence of atypical lymphocytosis, eosinophilia, or hepatic or renal involvement. As the pharmacologic treatment and management for COVID-19 patients continues to rapidly evolve, it is essential to consider adverse drug reactions on the differential for COVID-19 patients who present to the ED with new or worsening symptoms. Correct Answer = c Explain why this is the correct answer (max. 500 characters) Features included in the RegiSCAR Diagnosis Score for DRESS include fever > 101.3 • F or > 38.5 • C (core) or >100.4 • F or >38 • C (axillary), enlarged lymph nodes (≥ 2 sites, ≥ 1 cm), atypical lymphocytosis, eosinophilia, skin rash (extent > 50%, at least 2: edema, infiltration, purpura, swelling, biopsy suggesting DRESS), and internal organ involvement. 2 Elevated CRP may be seen, but it is non-specific. Acute anemia, hyponatremia, and lymphopenia are not classic findings in DRESS. Therefore, eosinophilia is the best answer option.

Source Correct Answer = D The first step in a CADR is to initiate withdrawal of the offending medication. Treatment of CADR is symptomatic, consisting of topical corticosteroids and oral antihistamines (d). Oral corticosteroids, choice c, are frequently used, but there is no evidence of their efficacy to support usage. IV antibiotics are not indicated in this scenario (b). Choice a is correct, but in addition, symptomatic treatment is warranted with topical corticosteroids and oral antihistamines.

Source: https://www.ncbi.nlm.nih.gov/books/NBK533000/#

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Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.visj.2021.100979.

Drug reaction with eosinophilia and systemic symptoms (DRESS)

Hydroxychloroquine: drug information

A method for estimating the probability of adverse drug reactions

Image 3. Patient's anterior chst wall