Developed a pruritic nodule on the left upper arm and was diagnosed with aluminum granuloma secondary to repeated anthrax vaccinations; This case was obtained from a scientific literature on date 09SEP2020.  A 37-year-old woman "developed a pruritic nodule on the left upper arm and was diagnosed with aluminum granuloma secondary to repeated anthrax vaccinations" (PT: Injection site granuloma), following the administration of BioThrax (anthrax vaccine adsorbed).  Case report: A 37-year-old woman presented with a pruritic nodule on the left upper arm that was present for several years. She reported a similar lesion on her right upper arm, which was biopsied a year prior at a different institution. The biopsy report from her right arm rendered a differential diagnosis of langerhans cell histiocytosis (LCH) versus lymphocytoma cutis; however, the slides were not available for review. Physical examination found a 4-cm poorly demarcated reticulated hyperpigmented patch (left upper arm; 2-cm linear hypertrophic biopsy scar through the center of a 4-cm poorly demarcated reticulated hyperpigmented patch). Palpation of this area found a poorly circumscribed subcutaneous nodule. On the right arm, a large poorly demarcated reticulated hyperpigmented patch with an underlying subcutaneous nodule and a well-healed biopsy site from a year prior was appreciated. Because of suspicion of a neoplastic process, an excisional biopsy of the left arm lesion was performed. The clinical differential submitted with the biopsy specimen included LCH, lymphocytoma cutis, dermal hypersensitivity reaction, lymphoma, granulomatous process, and nodular amyloidosis.   On hematoxylin-eosin stain, biopsy of the left upper arm showed multiple pale-to-violaceous inflammatory nodules within the deep subcutis. On closer inspection, aggregates of macrophages with abundant, violaceous cytoplasm and admixed chronic inflammatory cells were identified. The violaceous color and granular nature of the cytoplasm within the histiocytes is quite striking on x40 magnification. The histologic features were very similar to those seen following post biopsy excisions when aluminum chloride is used for hemostasis. The initial histologic differential diagnosis included, but was not limited to, infectious etiology, LCH, reactive granular histiocytosis, Erdheim-Chester disease, and granular histiocytosis not otherwise specified. Immunohistochemical and cytochemical analysis of the sample stained positive for CD68 and periodic acid-Schiff, and negative for S-100, CD1a, Grocott methenamine silver, and Fite.  Upon further questioning, the patient reported a history of 9 doses of anthrax vaccine; 6 injections in her left arm and 3 in her right arm as part of her military deployment requirements. Per chart review, this was the only vaccination she had received multiple times in both arms within the last 5 years. Given the vaccination history and these histologic features, tissue blocks were sent for scanning electron microscopy with energy dispersive x-ray spectroscopy (SEM/EDX) to further evaluate the granule containing histiocytes, which showed that they contained aluminum. A diagnosis of aluminum granuloma secondary to repeated anthrax vaccination was rendered. Both nodules were excised, resulting in complete resolution and no recurrence at 1 year.  Author's comment: Injection site granulomas are a known but uncommon finding. Multiple causative vaccines have been reported in the literature including tetanus (Tetracoq), influenza, hepatitis B and more. Although these nodules have been reported in clinical trials with the anthrax vaccine, occurring in 36 percent, 34 percent, and 4 percent of cases with the first, second, and third doses administered, respectively, there is no way to discern what truly caused them. They can present as persistent, pruritic subcutaneous nodules postulated to be the result of a delayed, granulomatous hypersensitivity reaction to aluminum hydroxide containing vaccines. Aluminum, an adjuvant that prolongs the antibody response, is added to many vaccines. Here we report a new case of anthrax vaccine induced nodules, which demonstrates a reactive granular histiocytosis pattern.  Company Comment: A consumer developed a pruritic nodule on the left upper arm and was diagnosed with aluminum granuloma secondary to repeated anthrax vaccinations (injection site granuloma). This consumer has a history of receiving 9 doses of anthrax vaccine (6 in left arm and 3 in right arm) and this was the only vaccine received by her in the past five years. This consumer had nodule for a few years on left upper arm and she also had similar lesion on her right upper arm. Both nodules were excised which resulted in completed resolution of the event with no recurrence for one year. BioThrax has aluminum hydroxide as an adjuvant and injection site granuloma developed in this consumer over a period of time as a response to aluminum present in BioThrax. Injection site granuloma is unexpected and the causality of BioThrax is assessed as probable (attributed to aluminum hydroxide present in BioThrax).; Sender's Comments: A consumer developed a pruritic nodule on the left upper arm and was diagnosed with aluminum granuloma secondary to repeated anthrax vaccinations (injection site granuloma). This consumer has a history of receiving 9 doses of anthrax vaccine (6 in left arm and 3 in right arm) and this was the only vaccine received by her in the past five years. This consumer had nodule for a few years on left upper arm and she also had similar lesion on her right upper arm. Both nodules were excised which resulted in completed resolution of the event with no recurrence for one year. BioThrax has aluminum hydroxide as an adjuvant and injection site granuloma developed in this consumer over a period of time as a response to aluminum present in BioThrax. Injection site granuloma is unexpected and the causality of BioThrax is assessed as probable (attributed to aluminum hydroxide present in BioThrax).