Reactive arthritis; keratoderma blenorrhagicum in the setting of reactive arthritis triggered by the COVID-19 vaccine; This is a literature report. Case Reports, 2022; DOI:10.1016/j.jdcr.2022.04.026.  A case of Reactive arthritis (RA) favored to be triggered by the Pfizer BioNTech COVID-19 mRNA vaccine (BNT162b2).  A 49-year-old previously healthy male presented with progressively worsening skin lesions and arthritis. Roughly one week after receiving the first dose of the BNT162b2 COVID-19 vaccine, he developed a painful rash and swelling of the right foot, with progression of the rash to the left foot and penis. He did not have any preceding genitourinary or gastrointestinal symptoms. His primary care provider diagnosed a bacterial infection and prescribed a two-week course of doxycycline 100 mg twice daily. He then received a ten-day course of prednisone 20 mg daily for joint pains. Over the next two weeks he developed worsening arthritis of the shoulders, hands, and feet. At this time, he received prescriptions for gabapentin 600 mg and nifedipine  42 mg once daily for a presumed diagnosis of chilblains. The patient's cutaneous and systemic  symptoms persisted, and he experienced an unintentional weight loss of approximately twenty  pounds.  The patient presented to our emergency department approximately two months after the onset of  his rash. Physical examination revealed pink papulopustules and keratoderma on the plantar feet, extensive onycholysis, nail thickening, and subungual debris of the toenails, tender edema of the right foot and joints of the right hand, and a scaly erythematous plaque on the penis. Laboratory workup showed an elevated erythrocyte sedimentation rate and C-reactive protein. Blood and urine cultures were negative. HLA-B27 testing by flow cytometry was indeterminate. Further HLA-B27 genotyping was not performed; a definitive result was therefore not obtained. Additionally, the patient tested  negative for syphilis, HIV, chlamydia, and gonorrhea. Clinical images upon admission to the hospital: Papulopustules and hyperkeratotic plaques on the plantar feet. Onychodystrophy of the toenails. Erythema and edema of the right foot. Swelling of the proximal interphalangeal joint of the right fourth finger. Scaly erythematous plaque on the glans penis.  A punch biopsy of a pustule on the left foot showed psoriasiform epidermal hyperplasia, loss of  the granular cell layer, neutrophilic infiltration of the epidermis, and entrapment of neutrophils in the stratum corneum, findings typical for a psoriasiform diathesis. Small vessel  vasculitis of the dermal papillary microvasculature was also observed. Additional immunologic stains revealed vascular deposits of C4d and C5b-9, representing classical complement pathway activation as seen in an Arthus type III immune complex reaction. Human manufactured spike glycoprotein was identified within deep dermal microvessels.  These pathological findings led to a diagnosis of keratoderma blenorrhagicum in the setting of reactive arthritis triggered by the COVID-19 vaccine.  Histopathology of lesion tissue. Histopathologic image of lesion specimen showed irregular psoriasiform epidermal hyperplasia, parakeratotic scale, and an absent granular cell layer, in addition to extensive neutrophilic infiltration of the stratum corneum. Inflammatory changes were also noted within the dermis, C4d stain revealed extensive highlighting of the microvessels, indicative of classic complement pathway activation triggered by immune complex deposition. C5b-9 stain demonstrated a positive reaction in a granular array within microvessels. The endpoint of classic complement pathway activation is the formation of C5b-9. SARS-CoV-2 (COVID-19) Spike S1 Subunit Antibody. In reactive arthritis, immune complexes (in this case spike glycoprotein complexed to host-manufactured antibody) localize to the superficial microvessels of the skin. In this patient, since spike 84 glycoprotein was already bound by host-manufactured antibody in the superficial dermis, the 85 spike protein was not detected in the superficial dermal vasculature.  The patient experienced symptomatic improvement after two days of intravenous methylprednisolone 32 mg. He was discharged on oral prednisone and ibuprofen. He follows with rheumatology and continues to experience improvement with weekly methotrexate.  No follow-up attempts are possible; information about lot/batch number cannot be obtained. No further information is expected.; Sender's Comments: Based on the current available information, a possible contributory role of the suspect product to the development of events cannot be excluded.  The case will be reassessed if additional information becomes available. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees and Investigators, as appropriate.,Linked Report(s) : US-PFIZER INC-202200750545 Same article/ patient/different drug/event