Lupus-like Rash of Chronic Granulomatous Disease Effectively Treated With Hydroxychloroquine

Importantly, CGD patients also demonstrate immune-related inflammatory disorders, most commonly inflammatory bowel disease, IgA nephropathy, sarcoidosis, and juvenile idiopathic arthritis.³ In addition, both CGD patients and female carriers of X-linked CGD have been reported to demonstrate lupus-like rashes that share overlapping clinical and histologic features with the rashes seen in true discoid LE and tumid LE patients without CGD.^4-6 This lupus-like rash is more commonly observed in adulthood and in carriers, possibly secondary to the high childhood mortality rate of CGD patients.^4,6

De Ravin et al³ proposed that autoimmune conditions arising in CGD patients who have met established criteria for a particular autoimmune disease should be treated for that condition rather than consider it as a part of the CGD spectrum. This theory has important therapeutic implications, including initiating paradoxical corticosteroid and/or steroid-sparing immunosuppressive agents in this otherwise immunocompromised patient population. They reported a 21-year-old man with cutaneous LE lesions and negative lupus serologies whose lesions were refractory to topical steroids but responded to systemic prednisone, requiring a low-dose alternate-day maintenance regimen.³ Beyond the development of a true autoimmune disease associated with CGD, systemic medications, specifically voriconazole, have been implicated as an alternative etiology for this rash in CGD.⁷ While important to consider, our patient’s rash presented in the absence of any systemic medications, supporting the former etiology over the latter.

Our case demonstrates the utility of hydroxychloroquine to treat the lupus-like rash of CGD. Similarly, the lupus-like symptoms of female carriers of X-linked CGD, predominantly with negative lupus serologies, also have been reported to respond to hydroxychloroquine and mepacrine.^4,5,8-10 Interestingly, the utility of monotherapy with hydroxychloroquine may extend beyond treating cutaneous lupus-like lesions, as this regimen also was reported to successfully treat gastric granulomatous involvement in a CGD patient.¹¹

Chronic granulomatous disease often is fatal in early childhood or adolescence due to sequelae from infections or chronic granulomatous infiltration of internal organs. Residual reactive oxygen intermediate production was shown to be a predictor of overall survival, and CGD patients with 1% of normal reactive oxygen intermediate production by neutrophils had a greater likelihood of survival.¹² In this regard, the otherwise good health of our patient at the time of presentation was consistent with his initial nitroblue tetrazolium test showing some residual oxidative activity, emphasizing the phenotypic variability of this rare genetic disorder and the importance of considering CGD in the diagnosis of seronegative cutaneous lupus-like reactions.