單純皰疹病毒感染後龜頭固定型藥物過敏反應：病例報告及文獻回顧

李珮欣、劉展榮、歐建慧

國立成功大學醫學院附設醫院 泌尿部

Fixed Drug Eruption on the Penile Glans following Herpes Simplex Virus Infection - A Case Report and Literature Review

Pei-Hsin Lee, Chan-Jung Liu, Chien Hui Ou

Divisions of Urology, National Cheng Kung University Hospital, Tainan, Taiwan

Case presentation

    A 25-year-old male patient who had no known underlying diseases presented at our urologic department due to a painless ulceration on the glans, which developed a vesicle with associated discharge. Topical gentamicin ointment was prescribed for the lesions and examination for sexually transmitted diseases had been ordered. However, he subsequently developed urethral pain, inguinal, and suprapubic discomfort, prompting his return the following day.

Urinalysis revealed no evidence of urinary tract infection and serological tests for common sexually transmitted diseases, including Chlamydia, Neisseria gonorrhoeae, HIV, and syphilis, returned negative results. Phenazopyridine and tamsulosin were administered for symptomatic relief, but the patient's symptoms continued to progress, necessitating an emergency department visit at midnight.

    Upon examination, several painful well-demarcated irregularly shaped erythematous ulcers with whitish discharge and desquamation were noted on the penile glans. There were no accompanying signs of fever, inguinal lymphadenopathy, or oral mucosal involvement. The patient denied any history of trauma, contact irritants, or recent travel. A Tzanck smear test was performed and showed no multinucleated giant cell. The patient reported a stable sexual relationship with a single partner for three years, with no engagement in high-risk sexual behaviors. Ophthalmological evaluation did not reveal any ocular findings consistent with Behcet's disease.

    Upon review of his medical history, a similar episode had occurred one year prior, during which a positive HSV-1,2 IgM test result (1.154) was recorded. However, other tests for sexually transmitted diseases were negative, and the ulcer resolved within two weeks following oral acyclovir treatment. Despite a positive HSV-1,2 IgM test result (1.130) during the current episode, the viral nucleic acid detection of HSV-1, HSV-2 and VZV by polymerase chain reaction (PCR) based assays all showed negative.

The patient also recalled experiencing throat pain on the right side of his neck preceding the onset of penile ulceration. He sought treatment at an otorhinolaryngology clinic, where clindamycin, mefenamic acid, pseudoephedrine, and bromelain were prescribed for symptomatic relief. Oral clindamycin and mefenamic acid were considered potential culprits. Topical gentamicin ointment was initiated for genital ulcers, resulting in gradual symptomatic improvement over one week.
 

Figure 1. Well-demarcated irregularly shaped erythematous

ulcers with whitish discharge and desquamation
 

Figure 2. Lesion on penile glans one year ago:

well-demarcated erythematous patch with clustered vesicles

Discussion

    Fixed drug eruptions are characterized by type IV CD8+ memory T- cell mediated hypersensitivity reaction [1]. While they can affect individuals of all ages, they are more commonly observed in midlife [2] and tend to localize to the extremities, trunk, lips, and genitalia [3]. Lesions often recur at the same site [4] and typically appear within 30 minutes to 8 hours following re-exposure to the offending medication [5]. Over a hundred medications have been implicated, with antibiotics (sulfonamide antibiotics, nitroimidazoles, tetracyclines, quinolones, penicillins, macrolides, glycopeptides, cephalosporins) and nonsteroidal anti-inflammatory drugs (acetylsalicylic acid, ibuprofen, naproxen, mefenamic acid) being the most frequently reported culprits [6].

     Fixed drug eruptions usually present as a well-demarcated red to brown macule, which are mostly solitary. However, they could also be scattered or generalized. The numerous variation of the presentation had also been reported [7], making the diagnosis more indistinguishable. Besides, fixed drug eruptions occasionally appear at the previous trauma site, especially where of herpesvirus infection or reactivation [8]. Medication history preceded the fixed drug eruption should be reviewed thoroughly, including the types and routes of administration. Diagnosis is primarily clinical, and skin biopsy is generally unnecessary.

    For symptomatic relief, topical corticosteroids and systemic antihistamines may be employed. Prognosis is generally favorable with discontinuation of the offending agent, although repeated exposure may lead to more severe reactions. Patients should be advised to avoid known trigger medications [3].

Conclusion

    Fixed drug eruptions, although uncommon, present with a diverse range of manifestations, making diagnosis challenging. A comprehensive clinical assessment, meticulous physical examination, and detailed medication history are paramount for accurate diagnosis. Recurrent eruptions at previous lesion sites following medication use should raise suspicion for fixed drug eruptions. In patients with a history of HSV infection, fixed drug eruptions should be considered in the differential diagnosis for skin lesions occurring at prior lesion sites. Early recognition, cessation of culprit drugs, and appropriate symptomatic management are essential for achieving a favorable outcome.

1.         Mizukawa, Y., Y. Yamazaki, and T. Shiohara, In vivo dynamics of intraepidermal CD8+ T cells and CD4+ T cells during the evolution of fixed drug eruption. British Journal of Dermatology, 2008. 158(6): p. 1230-1238.

2.         Anderson, H.J. and J.B. Lee, A Review of Fixed Drug Eruption with a Special Focus on Generalized Bullous Fixed Drug Eruption. Medicina, 2021. 57(9): p. 925.

3.         Flowers, H., et al., Fixed drug eruptions: presentation, diagnosis, and management. Southern medical journal, 2014. 107(11): p. 724-727.

4.         Shimizu, R., et al., Fixed Drug Eruption Associated with Nonsteroidal Anti-Inflammatory Drugs for Menstrual Pain: A Case Report. Case Reports in Dermatology, 2022. 14(1): p. 6-11.

5.         Ozkaya, E., Fixed drug eruption: state of the art. J Dtsch Dermatol Ges, 2008. 6(3): p. 181-8.

6.         McClatchy, J., et al., Fixed drug eruptions - the common and novel culprits since 2000. J Dtsch Dermatol Ges, 2022. 20(10): p. 1289-1302.

7.         Agarwal, A., et al., Uncommon variants of fixed drug eruption. Indian J Dermatol Venereol Leprol, 2023. 89(3): p. 475-481.

8.         Mizukawa, Y. and T. Shiohara, Which term should be used to describe drug eruptions confined to sites of previous herpes zoster lesions, ‘isotopic response’ or ‘recall phenomenon’? Clinical and Experimental Dermatology, 2004. 29(3): p. 323-323.