Age: 58.0
Sex: M
Vaccine: COVID19
Symptoms: Alanine aminotransferase, Aspartate aminotransferase, Bacterial test, Blood alkaline phosphatase, Blood calcium
Clinical narrative: disseminated histoplasmosis; This literature-non-study case was reported in a literature article and describes the occurrence of HISTOPLASMOSIS DISSEMINATED (disseminated histoplasmosis) in a 58-year-old male patient who received mRNA-1273 (Moderna COVID-19 Vaccine) for COVID-19 prophylaxis.   LITERATURE REFERENCE:     Previously administered products included for Multiple sclerosis: dimethyl fumarate (due to injection fatigue, he switched treatment to per os (PO) dimethyl fumarate which he discontinued a year later due to reported increased fatigue as a side effect.) in January 2014 and glatiramer acetate (injections discontinued due to fatigue.) until January 2014. Past adverse reactions to the above products included Fatigue with dimethyl fumarate and glatiramer acetate. Concurrent medical conditions included Multiple sclerosis (Diagnosed at age 46 supported by MRI and cerebrospinal fluid data.) since 2012, Lymphocytopenia and Immunosuppression. Concomitant products included FINGOLIMOD and GLATIRAMER ACETATE for Multiple sclerosis.   In March 2021, the patient received first dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) 1 dosage form. In April 2021, received first dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) dosage was changed to 1 dosage form. In September 2021, received first dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) dosage was changed to 1 dosage form. In 2021, the patient experienced HISTOPLASMOSIS DISSEMINATED (disseminated histoplasmosis) (seriousness criteria hospitalization and medically significant). The patient was treated with AMPHOTERICIN B (AMPHOTERICIN-B) (intravenous use) at a dose of 3 milligram/kilogram once a day; ITRACONAZOLE (oral use) at a dose of 200 milligram three times a day and ITRACONAZOLE (oral use) at a dose of 100 milligram twice a day. In 2023, HISTOPLASMOSIS DISSEMINATED (disseminated histoplasmosis) had resolved.      DIAGNOSTIC RESULTS (normal ranges are provided in parenthesis if available): In 2012, Magnetic resonance imaging: diagnosis of multiple sclerosis. In 2021, Alanine aminotransferase (0-55 U/L): 59 U/L Elevated. In 2021, Aspartate aminotransferase (5-40 U/L): 56 U/L Elevated. In 2021, Bacterial test: Negative. In 2021, Blood alkaline phosphatase (40-150 U/L): 189 U/L Elevated. In 2021, Blood calcium (8.4-8.4 mg/dl): 12.0 mg/dl High. In 2021, Blood culture: positive for histoplasma. In 2021, Blood parathyroid hormone (16-77 pg/ml): 8 pg/ml. In 2021, Computerised tomogram abdomen: unremarkable. In 2021, Computerised tomogram pelvis: unremarkable. In 2021, Computerised tomogram thorax: unremarkable. In 2021, Cryptococcus test: Negative. In 2021, Full blood count: normal range. Tested before COVID-19 vaccination. In 2021, Hepatitis viral test: negative. In 2021, Liver function test: normal range. Tested before COVID-19 vaccination. In 2021, Lymphocyte count: were persistently low.. In 2021, Platelet count (135-371 thousand per microlitre): 80 thousand per microlitre reduced. In 2021, SARS-CoV-2 test: Negative. In 2021, Urine antigen test: (Positive) positive for histoplasma. In August 2023, Urine antigen test: (Negative) Urine histoplasma was monitored serially until found to be negative in February and August 2023 (six months following antifungal treatment discontinuation).. In March 2024, Magnetic resonance imaging: multiple sclerosis remained clinically and radiologically stable. On an unknown date, Blood alkaline phosphatase (40-150 U/L): 190 U/L. On an unknown date, Blood calcium (8.4-8.4 mg/dl): 13.9 mg/dl Elevated. On an unknown date, Computerised tomogram thorax: showed diffuse ground glass opacity with patchy consolidation in the lung bases, suggesting fungal or viral pneumonia.. On an unknown date, Lymphocyte count: up-trending, and nearly close to normal limits.     For mRNA-1273 (Moderna COVID-19 Vaccine) (Unknown), the reporter did not provide any causality assessments.  Company comment: This literature case concerns a 58-year-old, male patient with medical history of multiple sclerosis on treatment with fingolimod and chronic lymphocytopenia, who experienced the unexpected serious (medically significant) event of disseminated histoplasmosis. The first symptoms in for of fatigue occurred few days after the third dose of mRNA-1273 with symptom of fever occurring approx. 2 months after 3rd dose but with final diagnosis of disseminated histoplasmosis being made approx. 4 months after vaccination. As reported, the patient received three doses of the Moderna COVID-19 vaccine (mRNA-1273). At the time of these vaccinations, he was taking 0.5 mg fingolimod every other day. A few days after the third dose, he noted the onset of a new fatigue, which was initially thought to be a side effect of the COVID-19 vaccine. This fatigue persisted and worsened over time. In late November, he was noted to have a low-grade fever and to have lost 15 pounds of body weight. Thus, this prompted blood work for CBC with cell differentials and a complete metabolic panel. Elevated levels of calcium (13.9 mg/dL; normal limits: 8.410.5 mg/dL) and alkaline phosphatase (189 units/L; normal limits: 40150 units/L) were detected. He was referred to the emergency room (ER) and subsequently hospitalized. Patient was discharged with diagnosis of hypercalcemia due to supplementation and dehydration however over the following days, fatigue, muscle aches, and low-grade fever persisted. A urine search for the antigen for histoplasma was performed and found to be positive. Blood culture was also showing positive for histoplasmosis and CT findings of diffuse ground glass opacity with patchy consolidation in the lung bases, suggesting fungal or viral pneumonia and symptoms of shortness of breath were observed. Fingolimod was discontinued and patient was initially treated for 3 days with Amphotericin B and later itraconazole with resolution of event. Authors stated that report describes rare possibility of serious infections in the setting of fingolimod-induced immunosuppression. It also suggests the importance of timely investigations of alternative diagnoses for post-vaccination-like symptoms in people with MS and immunosuppression. While initially attributed to lingering vaccination side effects, in retrospect, authors argue that in this immunocompromised person with MS, this worsening fatigue could have been due to the start of infection with histoplasmosis. Per authors although the immunological response to COVID-19 vaccination in this immunocompromised patient might have favored the occurrence of histoplasmosis, considering several alterations in the immune system have been shown to occur up to four weeks after the administration of the COVID-19 vaccine, there is insufficient evidence in this case to draw any firm conclusions regarding a pathogenic link between the vaccine administration and the occurrence of disseminated histoplasmosis. Considering the underlying immunosuppression as the main risk factor and the infectious nature of event causality is assessed as not related to mRNA-1273 per Company assessment. The benefit-risk relationship of mRNA-1273 is not affected by this report.   In 2012, Patient was diagnosed with multiple sclerosis when he presented to an outside hospital with subacute onset of left lower extremity weakness. After treatment with unspecified steroids, he started SC injections of glatiramer acetate. In Jan 2014, due to injection fatigue, he switched treatment to (PO) dimethyl fumarate which he discontinued a year later due to reported increased fatigue as a side effect. In January 2015 he started fingolimod.  In 2021, he received 3 doses of Moderna COVID-19 vaccine. A few days after the third dose, onset of a new fatigue was noted, which was initially thought to be a side effect of the COVID-19 vaccine. This fatigue persisted and worsened over time. In late November, he has a low-grade fever and lost 15 pounds of body weight. He was referred to ER and subsequently hospitalized. He received an unspecified IV fluids and his calcium level normalized. He was discharged home with the diagnosis of hypercalcemia due to increased intake of supplements and dehydration. Over the following days, fatigue, muscle aches, low-grade fever persisted.  An unspecified IV fluids along with amphotericin-B IV daily were maintained for 3 days. As his condition rapidly improved, he switched to itraconazole and was subsequently discharged. He continued itraconazole for 12 months. Fingolimod was discontinued and replaced with glatiramer acetate. At the time of this manuscript draft, 33 months from symptom onset, his MS has remained stable. The ALC values are up-trending and nearly close to normal limits.  Author concluded that report informs clinicians of rare possibility of serious infections in the setting of fingolimod-induced immunosuppression. It also suggests importance of timely investigations of alternative diagnoses for post-vaccination-like symptoms in people with MS and immunosuppression