Cutaneous Small Vessel Vasculitis Following Anti-Rabies Vaccine

Dear Editor, A 28-year-old male visited the dermatology outpatient department with a complaint of multiple red lesions on both limbs. The lesions had appeared 5 days ago and were accompanied by arthralgia. The patient denied any history of fever, previous infection, or drug intake. Five days prior to the onset of these lesions, the patient had been bitten by a dog on the left side of the leg (Level 3 bite with bleeding) and subsequently received a Rabies vaccine (Rabipur®, Valneva UK Limited, UK), with half of the dose administered around the bite site and the remainder in the left gluteal region (Day 0). The second dose (Day 3) of the vaccine led to erythema predominantly around the bite site, which gradually involved the other limb over 2 days. Concerned about the progression of symptoms, the patient sought medical attention and was advised to rest in bed [Figure 1a]. The purpura had nearly resolved when the patient received the third dose of the anti-rabies vaccine on the seventh day, after which intense erythema and palpable purpura developed again [Figure 1b].Figure 1: (a) Mild palpable purpura over the bilateral lower limbs following 2nd dose of Anti-rabies vaccine (b) Severe erythema and purpura after 3rd dose of Anti-Rabies vaccine (c) Complete subsidence of purpura after therapyOn examination, palpable petechiae and purpuric macules were observed on both lower limbs, with a greater prominence on the left distal limb around the bite site. A 4-mm skin biopsy was performed, and the patient was instructed to rest with elevated legs while being prescribed Oral prednisolone 30 mg once daily for 5 days. Routine laboratory tests including urine analysis, anti-nuclear antibodies, anti-streptolysin O titer, and complete blood count were all within normal limits. The erythrocyte sedimentation rate was 22 mm/hr. The histopathological examination using H and E staining showed perivascular neutrophilic infiltrate, foci of leucocytoclasia, nuclear dust, fibrinoid necrosis, and focal occlusion of small vessels with extravasation of red blood cells in the upper dermis [Figure 2a and b]. The purpura eventually resolved without leaving any residual pigmentation [Figure 1c]. The patient was advised to proceed with the fourth dose of the anti-rabies vaccine on day 30, following the standard vaccination schedule.Figure 2: (a) Upper dermis showing perivascular neutrophilic infiltrate, focal vessel occlusion [H and E, 10×], (b) with fibrinoid necrosis, nuclear dust and extravasation of red blood cells. [H and E, 40×]Rabipur® is a type of inactivated vaccine made from the Flury low-egg-passage (LEP) rabies virus strain. It is produced using purified chick embryo cell culture (PCEC). The vaccine vial contains various components, including chicken proteins, human albumin, neomycin, chlortetracycline, and amphotericin B.[1] Among these components, amphotericin B is reported to cause cutaneous leucocytoclastic vasculitis and local site reactions in an isolated case, reported by Cagatay et al.[2] However, the authors reported its appearance after almost 2 months of therapy.[2] Commonly reported side effects of the Rabipur® vaccine include anaphylaxis, headache, dizziness, nausea, vomiting, and urticaria. In rare cases, side effects such as encephalitis, Guillain-Barré syndrome, syncope, and angioedema may occur.[1] Cutaneous vasculitis has been documented in association with various viral vaccines, including those administered for COVID-19, influenza, hepatitis A, hepatitis B, and human papillomavirus.[3,4] Several mechanisms of viral-induced autoimmunity have been proposed, including effects on immune cell activation, cytokine profile, autoantibody production, molecular mimicry, and alteration of host antigens. Most reported adverse autoimmune reactions to the rabies vaccine have been neurological, with autoantibodies against brain white matter, myelin basic protein, and cardiolipin.[5] Based on our literature search, this is the first reported case of cutaneous vasculitis specifically linked to the anti-rabies vaccine. In cases where cutaneous small vessel vasculitis occurs as a result of vaccines or medications, it typically follows a mild course. It is important to note that the presence of cutaneous vasculitis does not warrant discontinuation of the vaccine regimen, especially when it is aimed at preventing a severe condition such as rabies. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published, and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.