Hydroxychloroquine-Induced Nonthrombocytopenic Purpura: A Case Series

May 2024 | Volume 23 | Issue 5 | 7781 | Copyright © May 2024


Published online April 10, 2024

Kawaiola Cael Aoki MASa, Gregory Bartos DOb, Stanley Skopit DO MSE FAOCD FAADc

aDr. Kiran C. Patel College of Osteopathic Medicine, Davie, FL 
bPGY-4 Dermatology Residency Training Program, LCH/LECOM, South Miami, FL
cDania Dermatology, Dania Beach, FL

Abstract
Hydroxychloroquine (HCQ) is a disease-modifying anti-rheumatic medication for the treatment of various autoimmune conditions. A rare side effect of HCQ is thrombotic thrombocytopenic purpura (TTP). We present two cases of patients who developed purpura that did not meet TTP criteria following treatment with HCQ. While the etiology of HCQ-associated TTP is poorly understood, we propose a spectrum of manifestations related to HCQ, ranging from benign purpura to TTP. As multiple factors contribute to the disease, we believe that HCQ may act as a "second hit" in patients with genetic susceptibility, which also influences the variability in the severity of disease manifestations.

J Drugs Dermatol. 2024;23(5):e124.     doi:10.36849/JDD.7781e

INTRODUCTION

Hydroxychloroquine (HCQ) is a 4-aminoquinoline used to treat malaria and as a disease-modifying agent in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).1 Side effects associated with using HCQ include cardiomyopathy and hematological reactions such as thrombocytopenia, agranulocytosis, leukopenia, aplastic anemia, and hemolysis in patients with glucose-6-phosphate deficiency.2,3 Additionally, it can cause blue-gray hyperpigmentation of the head, forearms, mucosa, nails, and other areas of the skin, which may be mistaken for abuse in the elderly.1 

HCQ is an amine acidotropic form of quinine, a common drug related to the etiology of thrombotic thrombocytopenic purpura (TTP) that causes quinine-dependent antibodies that react with platelets and other cells.4 Cases of HCQ-associated TTP have been previously reported in the United States,5,6 Netherlands,3,7 Turkey,4,8 and Spain.9 However, hydroxychloroquine-associated purpura without thrombocytopenia has yet to be solely described in the literature. We present a case series of two patients who developed purpura that did not meet the criteria for TTP following treatment with hydroxychloroquine.

CASE 1: GN

A 58-year-old female presented to the clinic for a biopsy-proven, recalcitrant eruptive granuloma annulare on the torso and proximal thighs. The patient was prescribed oral hydroxychloroquine 200 mg twice daily and instructed to follow up in one month. Two weeks later, topical clobetasol 0.05% cream and oral prednisone taper over 6 weeks were added due to the progression of cutaneous lesions. Six weeks after her initial visit, the eruptive granuloma annulare responded to treatment, however, the patient developed multiple areas of blood-tinged reddish to purple pigmentation in an irregular pattern bilaterally on the anterior lower legs (Figure 1). 



A diagnosis of solar purpura was suspected. Approximately 10 weeks from the initial visit, the patient had worsening purpura (Figures 2 and 3) and a 4-mm punch biopsy from the right anterior lower leg was obtained (Figure 4), and bloodwork was ordered. It was suspected that hydroxychloroquine and prednisone caused the purpura. The patient was instructed to stop the hydroxychloroquine and continue clobetasol twice daily until the next visit.