Red scrotum syndrome: Successful treatment with oral carvedilol in two patients

Dear Editor,

Red scrotum syndrome (RSS) is a chronic inflammatory skin condition of the anterior half of the scrotum and it represents a therapeutic challenge.^1-2 We present two RSS cases, refractory to oral ivermectin, who responded to oral carvedilol with prolonged remission

An otherwise healthy 29-year-old man consulted with pain and itching in the genital area for 4 months. He had been unresponsive to topical corticosteroids methylprednisolone aceponate 1mg/g/d for two months and antifungals (clotrimazol 1% once daily application for 2 months). Topical tacrolimus 0.1% therapy showed a modest improvement. The visual analogue scale (VAS) score was 9 (0-10), and the dermatology life quality index (DLQI) was 30 (0-30). Physical examination revealed erythema of the scrotum with no other skin lesions. Dermoscopy revealed erythema and some unfocused telangiectatic vessels. RSS was diagnosed, topical corticosteroid was discontinued, and oral ivermectin (200 µg/kg per week for 4 weeks), together with topical tacrolimus (0.1%), was initiated. Over the following 4 weeks, symptoms reduced, achieving a VAS of 2 and a DLQI of 10. However, after 2 months, symptoms reappeared with a VAS of 7 and a DLQI of 20. Oral carvedilol (6.25 mg/day) was started, and topical tacrolimus (0.1%) was continued. Improvement was observed during the following month. Twelve months later, the patient continues to be under treatment, maintaining an excellent clinical response (VAS 1, DLQI 4). He did not suffer from any adverse effects.

A 70-year-old man with a history of hypertension and psoriasis reported 12 months of genital pain and pruritus recalcitrant to topical corticosteroids, topical antifungals, topical tacrolimus and oral itraconazole. The discomfort was causing work and social disruption. VAS was 9, and DLQI was 24. Physical examination revealed erythema on the scrotum and penile shaft and lesions of psoriasis on the groins. Dermoscopy revealed erythema and some unfocused telangiectatic vessels. A diagnosis of RSS was established. Following discontinuation of topical corticosteroids, oral ivermectin (200 µg/kg per week for 5 weeks) together with topical tacrolimus (0.1%) induced a notable symptom reduction over the following 4 weeks (VAS 3, DLQI 10). However, symptoms intensified after 3 months (VAS 7, DLQI 18). Oral carvedilol (6.25 mg/day) was started, and topical tacrolimus (0.1%) was continued, leading to a reduction of symptoms over the subsequent 4 weeks (VAS 2, DLQI 4). The treatment was continued for the following 12 months. A complete response was maintained, and no adverse effects were reported.

RSS is a complex disorder. Its pathogenic mechanisms include neuro-vascular/neurogenic inflammation, microbial films, dysregulation of neurotransmitters, and topical corticosteroids discontinuation.³ Differential diagnosis includes contact dermatitis, fungal infections, atopic or seborrheic dermatitis, and psoriasis.

RSS represents a therapeutic challenge. Discontinuation of topical corticosteroids is paramount. Studies on RSS therapy are limited, and we have only found case reports and case series [Supplementary Table S1]. The most frequently prescribed treatment was oral doxycycline, either alone or in combination with other treatments, followed by steroid abstinence alone and pregabalin. Calcineurin inhibitors showed higher effectiveness when combined with systemic doxycycline. Topical timolol (0.5%) gel was used in one patient with rapid response (2 weeks).⁴ Oral ivermectin followed by topical ivermectin may constitute an effective treatment in some cases.⁵ Three cases have been reported using oral carvedilol [Table 1]. Complete response was maintained after 24 weeks with no adverse effects.

Carvedilol is a non-selective, β-adrenergic blocking agent and a weak α1-antagonist receptor. It has antioxidant and anti-inflammatory effects. Its vasoconstrictor effect could be the mechanism responsible for its effectiveness in RSS. It is used in RSS at low doses (6.25 mg once daily or twice daily), compared to standard doses of 25 to 50 mg/day for patients with heart failure. Rare adverse effects at higher doses include hypotension and bradycardia, although it is well tolerated in elderly patients.⁶ Other cutaneous diseases with a pathogenic mechanism similar to RSS in which low-dose oral carvedilol has been effective are red vulva syndrome, rosacea, and erythromelalgia.⁷

Different management strategies have been proposed for RSS with variable results. Low-dose oral carvedilol may be a well-tolerated alternative for this disorder.