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

To the Editor:

A 26-year-old man was referred to our clinic for evaluation of a persistent red rash to rule out cutaneous lupus erythematosus (LE). The patient was diagnosed at 12 years of age with autosomal-recessive chronic granulomatous disease (CGD)(nitroblue tetrazolium test, 5.0; low normal, 20.6), type p47^phox mutation. At that time the patient had recurrent fevers, sinusitis, anemia, and noncaseating granulomatous liver lesions, but he lacked any cutaneous manifestations. The patient was then treated for approximately 2 years with interferon therapy but discontinued therapy given the absence of any signs or symptoms. He remained asymptomatic until approximately 16 years of age when he experienced the onset of an intermittently painful and pruritic rash on the face that slowly spread over the ensuing years to involve the trunk, arms, forearms, and hands. Although he reported that sunlight exacerbated the rash, the rash also persisted through the winter months when the majority of the sun-exposed areas of the trunk and arms were covered. He denied exposure to topical products and denied the use of any oral medications (prescription or over-the-counter).

Review of systems was negative for fever, fatigue, malaise, headaches, joint pain, arthritis, oral ulcers, dyspnea, or dysuria. Physical examination revealed a well-defined exanthem comprised of erythematous, mildly indurated papules coalescing into larger plaques with white scale that were exclusively limited to the photodistributed areas of the face (Figure 1), neck, arms, forearms, hands, chest, and back. Laboratory test results included the following: minimally elevated erythrocyte sedimentation rate of 31 mm/h (reference range, 0–15 mm/h) and rheumatoid factor of 45 IU/mL (reference range, <20 IU/mL; negative antinuclear antibody screen, Sjögren syndrome antigens A and B, double-stranded DNA, anti–extractable nuclear antigen antibody test, and anti-Jo-1 antibody; complete blood cell count revealed no abnormalities; basic metabolic panel, C3 and C4, CH50, glucose-6-phosphate dehydrogenase activity, total plasma porphyrins, and testing for hepatitis B and C virus and human immunodeficiency virus serologies were negative. Skin biopsy from a lesion on the lateral arm showed features consistent with interface dermatitis (Figure 2). Additional skin biopsies for direct immunofluorescence showed linear deposition of IgG at the dermoepidermal junction, both from involved and uninvolved neck skin (more focally from the involved site). Extensive photopatch testing did not show any clinically relevant positive reactions.

Figure 1. Erythematous patches and thin plaques in photodistributed areas on the face, with sparing of the nasolabial folds. Figure 2. A biopsy from the right lateral arm showed basal layer vacuolization; scattered individually necrotic keratinocytes (black arrows; H&E, original magnification ×400 [inset]); increased dermal mucin; and a mild superficial, predominantly perivascular, lymphocytic infiltrate with mild leukocytoclasis and focal extravasated erythrocytes (H&E, original magnification ×100).

Given the patient’s history of CGD and the extensive negative workup for rheumatologic, photoallergic, and phototoxic causes, the patient was diagnosed with a lupus-like rash of CGD. The rash failed to respond to rigorous sun avoidance and a 3-week on/1-week off regimen of high-potency class 1 topical steroids to the trunk, arms, forearms, and legs, and lower-potency class 4 topical steroid to the face, with disease flaring almost immediately on cessation of treatment during the rest weeks. Given the marked photodistribution resembling subacute cutaneous LE, oral hydroxychloroquine 200 mg (5.7 mg/kg) twice daily was initiated in addition to continued topical steroid therapy.

Four months after the addition of hydroxychloroquine, the patient showed considerable improvement of the rash. Seven months after initiation of hydroxychloroquine, the photodistributed rash was completely resolved and topical steroids were stopped. The rash remained in remission for an additional 24 months with hydroxychloroquine alone, at which time hydroxychloroquine was stopped; however, the rash flared 2 months later and hydroxychloroquine was restarted at 200 mg twice daily, resulting in clearance within 3 months. The patient was maintained on this dose of hydroxychloroquine.

During treatment, the patient had an episode of extensive furunculosis caused by Staphylococcus aureus that was successfully treated with a 14-day course of oral doxycycline 100 mg twice daily. He has since been maintained on prophylactic intranasal mupirocin ointment 2% for the first several days of each month and daily benzoyl peroxide wash 10% without further episodes. He also developed a single lesion of alopecia areata that was successfully treated with intralesional steroid injections.

Chronic granulomatous disease can either be X-linked or, less commonly, autosomal recessive, resulting from a defect in components of the nicotinamide adenine dinucleotide phosphate oxidase complex that is necessary to generate reactive oxygen intermediates for killing phagocytosed microbes. Cutaneous manifestations are relatively common in CGD (60%–70% of cases)¹ and include infectious lesions (eg, recurrent mucous membrane infections, impetigo, carbuncles, otitis externa, suppurative lymphadenopathy) as well as the less common chronic inflammatory conditions such as lupus-like eruption, aphthous stomatitis, Raynaud phenomenon, arcuate dermal erythema, and Jessner lymphocytic infiltrate.² The pathognomonic clinical feature of CGD is the presence of characteristic multinucleated giant cell granulomas distributed in multiple organ systems such as the gastrointestinal system, causing pyloric and/or small bowel obstruction, and the genitourinary system, causing ureter and/or bladder outlet obstruction.³