Introduction:Malignant syphilis (MS) is a rare and severe variant of secondary syphilis that is frequently associated with HIV infection.The clinical impact of HIV and syphilis co-infection is bidirectional,and the presence of MS is associated with acute HIV infection.Clinically,MS is characterized by nodular and ulcerative lesions affecting the trunk and extremities,which are covered with thick crusts.The treatment of choice for MS remains benzathine penicillin G.Herein,we report a case in which MS was the initial presentation of HIV infection.Case presentation:A 35-year-old male patient came with the chief complaint of extensive erythematous nodular rash for the past one month,with notable ulceration on some lesions with annular configuration along with fever and malaise.Based on the abovementioned clinical,laboratory,and histopathologic findings,the patient was diagnosed with MS and HIV.The diagnosis was established based on histopathological examination and syphilis serological testing.Discussion:Cutaneous disorders are a frequent presenting feature of HIV infection.The clinical manifestations of syphilis in immunosuppressed patients are often severe and/or atypical.The patient was then treated with weekly intramuscular administration of 2.4 million units of benzathine penicillin G for 3 weeks and achieved rapid and significant clinical improvement,with no Jarisch-Herxheimer reaction.Conclusion:Co-infection with syphilis and HIV alters the course of both diseases,and most HIV-infected patients with syphilis have typical disease manifestations associated with decreased CD4+ T-cell counts.