Genital allergy should be considered as a possible diagnosis in all patients with genital soreness or irritation for which no infection or dermatosis can be identified and in whom symptoms remain unchanged or worsen with treatment. It is an underreported and underdiagnosed condition as patients may not complain about symptoms in this area. Moreover, diagnosis and therapy may not often be conducted by a dermatologist or allergologist. Therefore, many cases of allergic diseases in the genital area remain undetected.

Perigenital warty lesions can be of diverse origin. An attempt should be made to rule out sexually transmitted disease (STD). If the diagnosis is not settled, biopsy may clinch the diagnosis.

HIV/AIDS-related immune alteration poses many diagnostic and therapeutic challenges. HIV-positive 44-year-old male, on second-line antiretroviral therapy (ART) presented with asymptomatic non healing, well-defined, erythematous ulcer over penis since 8 months with serosanguinous discharge. Inguinal lymph nodes were not palpable. Tzanck smear was negative. Biopsy was not done as the patient was not willing for the same. Acyclovir was given considering herpes infection to which there was no response, and hence azithromycin and metronidazole were given, without improvement. Minocycline was given to take care of possible atypical mycobacterial infection. Due to lack of response, corticosteroid was given for 2 weeks keeping in mind possibility of vasculitis, but there was no improvement. Although investigations to rule out tuberculous etiology were negative, empirical anti-Koch's therapy Category 2 was given without response even after 3 months. Finally, a biopsy was taken from lesion which was suggestive of donovanosis. Trimethoprim Sulfamethoxazole in higher dose was started to which he responded after 2 weeks, and therapy was continued till complete response. Patient is on second-line ART for last 7 years. He is clinically stable, but his CD4 count is hovering at around 250–300 suggestive of ART failure. Virological evaluation was not feasible. Diagnostic challenges posed include possibility of resistant bacterial, viral infection, vasculitis, or drug reaction in a setting of probable ART failure.

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