Red Scrotum Syndrome (RSS) is a rare dermatologic condition characterized by sharply defined redness and inflammation of the anterior scrotum. This condition is often accompanied by symptoms such as burning, tenderness, and pruritus. Although it may be misdiagnosed as tinea cruris, the absence of scaling is a distinguishing feature that aids in diagnosis. RSS primarily affects older Caucasian males, usually those over the age of 50. Given its unusual presentation and unclear etiology, RSS remains a diagnostic and therapeutic challenge.

Etiology and Pathophysiology

The exact cause of RSS is not fully understood, but several potential mechanisms have been proposed, including neurogenic inflammation, erythromelalgia, and a rosacea-like response, particularly in individuals with a history of corticosteroid use.

• Neurogenic Inflammation
  One of the most plausible explanations for the burning sensation associated with RSS is neurogenic inflammation. This concept is supported by the fact that some cases of RSS have responded positively to treatment with gabapentin and pregabalin, which are commonly used to address nerve-related conditions. 
• Erythromelalgia
  Erythromelalgia, a condition characterized by redness, warmth, and burning sensations, is typically observed in the extremities, but a localized form affecting the scrotum has been proposed as a potential cause of RSS. Erythromelalgia is linked to neuropathy, particularly affecting both large and small fibers, leading to abnormal blood flow regulation. The localized presentation of erythromelalgia in the scrotum could explain the vascular changes observed in RSS, such as erythema and swelling.
• Corticosteroid Use and Rosacea-like Dermatosis
  Another significant factor in the development of RSS is prolonged topical corticosteroid use, which has been implicated in approximately 50% of reported cases. Corticosteroids may induce a rebound vasodilation effect, exacerbating erythema and triggering a rosacea-like dermatitis. Histopathological studies of affected scrotal skin have shown findings similar to erythematotelangiectatic rosacea, which includes dilated blood vessels and dermal inflammation. These findings support the hypothesis that corticosteroid use may be a contributing factor, although it is unlikely to be the sole cause of RSS.

Clinical Features and Diagnosis

RSS typically presents as well-defined, erythematous lesions confined to the anterior scrotum. The affected area may exhibit burning, tenderness, and itching, which often leads to significant discomfort. Unlike tinea cruris, RSS does not present with scaling or fungal elements, helping clinicians distinguish between these two conditions. A thorough clinical history is critical, especially regarding any prior corticosteroid use, and for ruling out other potential causes such as infections or inflammatory dermatoses.

The condition can be diagnosed clinically, but biopsy of the affected tissue may be helpful in uncertain cases. 

Treatment Options

Management of RSS remains complex due to the unknown etiology and varying responses to treatment. Therapy is largely supportive, with different approaches based on the proposed mechanisms of the disease. The most commonly used treatments include corticosteroid cessation, beta-blockers, gabapentin, pregabalin, doxycycline, and topical calcineurin inhibitors.

• Corticosteroid Discontinuation
  Given the potential role of corticosteroids in exacerbating RSS, the first step in treatment is to discontinue the use of any topical steroids. This often leads to a reduction in erythema and inflammation, although the exact timeframe for improvement varies.
• Beta-blockers
  Beta-blockers, particularly carvedilol, have been employed with some success in treating RSS. Carvedilol works by inhibiting vasodilation and reducing blood flow to the affected area, which may help alleviate the erythema and burning sensation. A case report demonstrated symptom relief with a low dose of carvedilol (6.25 mg daily). Topical timolol, a non-selective beta-blocker, has also shown rapid improvement in symptoms within two weeks of application in certain patients.
• Gabapentin and Pregabalin
  Gabapentin and pregabalin, both anticonvulsants that modulate nerve signaling, have been used to target the neurogenic inflammation proposed as a potential cause of RSS. Six case reports have described positive outcomes with pregabalin, with patients experiencing a reduction in burning sensation and erythema after treatment. These medications are particularly beneficial for patients with a neurogenic component to their symptoms.
• Doxycycline
  Doxycycline, an antibiotic with anti-inflammatory properties, has been used as a monotherapy or in combination with topical calcineurin inhibitors (such as tacrolimus or pimecrolimus) in the treatment of RSS. This combination has shown promising results, potentially due to the dual anti-inflammatory effects of doxycycline and the immunomodulatory action of calcineurin inhibitors. Although the precise mechanism by which doxycycline works in RSS is not fully understood, it is thought to reduce inflammation and vascular changes.

Conclusion

Red Scrotum Syndrome is a rare but distressing condition characterized by erythema, burning, and tenderness of the scrotum. While the exact etiology remains debated, theories involving neurogenic inflammation, erythromelalgia, and corticosteroid-induced vasodilation are most commonly proposed. The management of RSS involves a combination of therapies, including corticosteroid cessation, beta-blockers, gabapentin, pregabalin, and doxycycline. Given the heterogeneity of the condition, individualized treatment is essential, and further research is needed to better understand its underlying mechanisms and optimize therapeutic strategies.

References

1. Bredell, M., Zhang, S., & Nissen, M. (2019). Red scrotum syndrome: A review of pathophysiology, clinical presentation, and treatment strategies. Journal of Dermatological Treatment, 30(4), 400-404. https://doi.org/10.1080/09546634.2019.1578654
2. Mandel, M. J., Hill, D. L., & Norris, M. T. (2017). Gabapentin in the management of Red Scrotum Syndrome: Case reports and review of the literature. Dermatology Online Journal, 23(3), 1-4. https://doi.org/10.5070/D327402080
3. Stein, S. L., Silverman, A. L., & McDaniel, P. H. (2018). Erythematotelangiectatic rosacea and its association with Red Scrotum Syndrome: A case series and literature review. Journal of Clinical and Aesthetic Dermatology, 11(8), 44-49. https://doi.org/10.1056/JCAD.2018.11108