Red Scrotum Syndrome Responding to Doxycycline: A Report of Two Cases with a Review of the Literature
Year: 2026
Type: article
Abstract: Dear Editor, Red scrotum syndrome (RSS) is a rare, chronic inflammatory condition characterized by persistent scrotum redness associated with itching, pain, or a burning sensation. Multiple drugs have been tried in the management of RSS, with variable outcomes. Herein, we report two cases of RSS responding to doxycycline monotherapy. Case 1: A 47-year-old man presented to the dermatology outpatient department with persistent redness of the scrotum associated with an intense burning sensation for 6 months. Cutaneous examination showed severe, well-demarcated erythematous plaques on the scrotal skin, extending onto the proximal penile shaft, with a sharp border separating it from the uninvolved skin. There was mild telangiectasia with no scaling or infiltration [Figure 1].Figure 1: Well-demarcated erythematous, painful lesion on the scrotumCase 2: A 38-year-old man presented with severe itching and burning pain on his scrotum for 1 year. He gave a history of application of potent topical corticosteroids on and off for scrotal dermatitis for the past 3 years. On examination, well-defined erythema of the scrotal skin and atrophic striae on the inner thighs were observed [Figure 2a].Figure 2: (a): Baseline photograph showing erythematous lesion on the scrotum at the initial visit. (b): Follow-up photograph showing resolution of erythema with doxycyclineThe chronic nature of the disease and its associated symptoms substantially impacted the patients’ quality of life. Both patients experienced difficulty performing daily activities, impairing personal functioning and social interactions. Both patients denied history of any trauma, bite, or application of any other topical agent over the area, apart from topical steroids in the second case. Differential diagnoses of contact dermatitis, tinea incognito, inverse psoriasis, Bowen’s disease, mycosis fungoides, and RSS were considered. Patch testing with the Indian standard series was done to rule out the possibility of contact dermatitis. Potassium hydroxide test yielded negative results, ruling out tinea incognito. Histopathology revealed acanthosis and parakeratosis without cellular atypia, hypergranulosis, or clubbing or elongation of rete ridges. The superficial dermis showed moderate inflammatory infiltration of lymphocytes, plasma cells, and occasional eosinophils. The nonspecific findings ruled out other differentials such as Bowen’s disease, mycoses fungoides, and inverse psoriasis [Figure 3]. Based on the clinical and histopathological features, a final diagnosis of RSS was made by exclusion.Figure 3: Photomicrograph shows acanthosis and parakeratosis without any hypogranulosis or elongation of rete ridges. The superficial dermis shows moderate inflammatory infiltrate of lymphocytes, plasma cells, and occasional eosinophils. [Hematoxylin and eosin stain, 100×]The patients were counselled about the relapsing nature of the disease and advised to avoid further topical corticosteroid application in the second patient. Additionally, oral doxycycline at a dose of 100 mg twice daily was started, along with antihistamines and bland emollients to alleviate symptoms that occurred during mild flare-ups after sudden withdrawal of steroids. The symptoms completely resolved within 4 weeks of treatment. The patients were maintained on doxycycline 100 mg once daily for 8 weeks, following which therapy was stopped. The patients are on regular follow-up without any severe flare-ups or relapses [Figure 2b]. RSS, also referred to as male genital dysesthesia, is not an uncommon disorder. It is characterized by erythema along with severe itching, burning sensation, or hyperalgesia on the scrotum, and is most commonly associated with prolonged corticosteroid use, usually in older men. It is considered akin to red skin syndrome, encompassing entities such as red face syndrome, vulvodynia, and/or anal atrophoderma. With the rising use of topical corticosteroids over the last century and the availability of over-the-counter combination creams across India, the incidence of this entity is on the rise. The impact of this disease on quality of life is substantial.[1] The exact pathophysiology of the disease is poorly understood. The initial hypothesis revolved around the possibility of erythromelalgia-like presentation, given the complaints of severe burning pain associated with redness and a feeling of increased warmth in the area. Successful use of neuropathic drugs such as amitriptyline and pregabalin supported this hypothesis.[2] Subsequently, the concept of “corticosteroid addiction,” attributing the associated symptoms to vasodilation mediated by nitric oxide produced by the vascular endothelium, was proposed by Rapaport et al.[3] A possibility of steroid-induced rosacea-like dermatitis was proposed by Byun et al.[4], given the history of chronic use of topical corticosteroids in the majority of patients with RSS. They hypothesized that both face and genital skin, being areas of highest steroid absorption, could precipitate a rosacea-like picture on prolonged usage. This hypothesis was supported by findings from a study by Narang et al.,[5] wherein histopathology of patients revealed ectatic venules and sparse perivascular infiltrate mimicking rosacea. In their study, long-term topical steroid usage was a common denominator among all patients, highlighting its role in disease pathogenesis. Given its diverse etiopathogenesis and variable response to treatment modalities—including neuropathic agents, anti-inflammatory drugs, and vasomodulators—multiple modalities have been tried based on their specific mechanism of action, targeting the disease process in RSS with variable outcomes [Table 1].[6-9] Doxycycline is a semi-synthetic tetracycline group of drugs that has been tried in various inflammatory conditions, such as acne and rosacea, apart from rheumatoid arthritis syndrome, due to its anti-inflammatory properties. It inhibits matrix metalloproteinase enzymes and decreases the proinflammatory cytokines involved in the disease process of RSS, thereby alleviating the symptoms and erythema. It is also known to inhibit the expression and increase the degradation of the nitric oxide synthetase enzyme, preventing further tissue damage.[10]Table 1: Review of literature of treatment modalities tried in red scrotum syndromeTo conclude, this report highlights the efficacy of doxycycline in the management of RSS and reviews the literature on this enigmatic condition, delving into its etiopathogenesis and the various therapeutic modalities that have been tried in the past. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Use of artificial intelligence (AI) The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Institution: Institute of Medical Sciences and Sum Hospital
Language: English
Subfield: Dermatology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7124934159