Age: 26.0
Sex: F
Vaccine: HPV4
Symptoms: Granuloma, Injection site nodule, Injection site pain, Laboratory test, Laboratory test normal
Clinical narrative: Information has been received from a pathologist concerning a female (age unknown), who, on an unspecified date, was vaccinated with a dose of Gardasil. The patient had received the vaccination and developed a tender nodule at the injection site. Subsequently, the patient died. The nodule was excised and the pathologist was researching possible granulomatosis with Gardasil. No product quality complaint was involved. Additional information has been requested.  08/03/07 Email to FDA/CDC: Spoke w/the reporter on this case who is quite upset that it has been mistakenly reported as a Death.  The reporter is a pathologist who had received a biopsy of the nodule.  She stated she called Merck just to ask a question as to whether granulomas at the injection site had occurred during clinical trials.  She emphatically stated that this patient did not die & she will not provide name/dob or any additional information.  Since Merck reported this case & discusses death in box 7 & in box 8, how would you like to handle this report?  Would someone at CDC/FDA want to contact Merck & ask for clarification on this report? 8/3/07 FDA will contact Merck to discuss case. 8/3/07 Email from Merck to FDA: We spoke to the pathologist who now states that the patient is  alive and well.  This followup will be sent via normal procedures on Monday but I wanted to send you this draft copy today. 8/6/07 Email from FDA to VAERS: Merck has confirmed that the pt is alive. 8/6/07 Status of report changed from death to serious.  Case closed as incomplete as no further information provided.  Case will be reopened should additional information become available. Initial and follow-up information has been received from a pathologist and authors of a published literature article concerning a 26 year old woman who was presented for an evaluation of a tender subcutaneous nodule on the outer aspect of her left upper arm which was presented for approximately 1 month. Two months before presentation the patient had received the third vaccination of the quadrivalent GARDASIL (in a series of 3) in that area. The patient's previous medical history was non contributory. Her surgical history included an appendectomy 1 years before which was complicated by pelvic peritonitis and exploratory laparatomy. Interstingly microscopic examination of her appendix demonstrated acute appendicitis with multiple opitheloid mural granulomas. Grocott's Methenamine Silver (GMS) and Acid-Fast bacteria (AFS) stains were negative for organisms. After surgery she developed spreading scars at the site of her appendictomy and laparatormy incisions and a work-ip with medical gentics was initiated. Both she and her brother were noted to have high arched paltes and joint laxity. Taken together, it was believed that she has a poorly characterized, mild forms of EHLERS-DANIOS syndrome. Physical examination revealed an exquisitely tender subcutaneous nodule measuring 1.3 cm. Clinically the lesion was suspected to be a hemangioma, arteriovenous malformation or panniculitis. The nodule was excised to the level of subcutaneous fat and sutured without incident. Routine histopathologic analysis demonstrated subcutaneous tissue containing numerous large area of necrosis surounded by pallisaede epitheloid histiocytes with oval nuclei and pale eosinophilic cytoplasm containing abundant violaceous/gray granular material. Histiocytes containing this violaceous granular material were abundant and arranged in sheets around the central foci of necrosis. These intracytoplasmic granules were diastase resistant periodic acid-Schiff (PAS) positive. Around the histiocytic sheets there was a rim of lymphoid cells and fibrosis. Multinucleated giant cells were rare and polarizable material was not detected. No organisms were seen using special stains for microorganisms, including diastase-PAS, GMS, Gram, Fite, AFS, and Steiner stains. Given the deep location and multinodular distribution of the granulomas the possibility of a rheumatoid nodule or deep granuloma anulare (pseudorheumatoid nodule) was considered. These were considered to be unlikely, however given the clinical presentation and the presence of the abundant diastase-PAS-positive violaccous granules within histiaocytes. The history of recent GARDASIL administration in the area of the granuloma prompted us to perform an ammonium aurintricarboxylate (Aluminum, Fisher Scientific) strain as previously described. The presence of aluminum was demonstrated within numerous histiocytes of the granulomas, confirming the diagnosis of an alumiunm granuloma. The patient recovered well from her procedure and has had no further complications. In this case the prior history of appendicitis with unusual granulomatous reaction is noteworthy. Granulomatous inflamation of the appendix is uncommon and can be caused by a variety of conditions, including systemic disorders such as CROHN disease and sarcoidosis and infections such as mycobacterium tuberculosis. Yersinis pseudotuberculosis, parasies and fungi. Because none of these associated disorders or inectious agents were demonstrated in this patient the findings were labeled as parted of an idiopathic granulomatous appendicitis. The relationship of this unusual reaction pattern in the appendix with the granulaomatous response to the aluminum containing vaccine in this case is unclear. In conclusion a case characterized by the presence of a persistent nodule at an injection site of GARDASIL showing a palisading granulomtous reaction to aluminum material. The presence of a subcutaneous granulomatous response mises a differential diagnosis that includes infection, reheumatoid nodule and deep granulotoma annulare. This case highlights the need to consider vaccine reactions as well, especially when the granulomas are found in an area commonly used in vaccine delivery such as the buttocks or deltoid. The patient did not die as previously reported. No product quality complaint was involved. The causality was unknown. Additional information has been requested.