Received Dec 31, 2025
| Type | Name | Manufacturer | Dose | Lot | Route / Site |
|---|---|---|---|---|---|
| COVID19 | COVID19 (COVID19 (PFIZER-BIONTECH)) | PFIZER\BIONTECH | 1 | — | — |
Herpes zoster; Safety information originally reported under manufacturer case PV202300164051 has been nullified and re-entered under this new manufacturer report number 202500251601. This is a literature report, Program ID: for the following literature source:. A 44-year-old woman developed Herpes zoster (HZ) during treatment with dimethyl fumarate and methylprednisolone for relapsing remitting multiple sclerosis (RRMS) and following vaccination with tozinameran against COVID-19 [not all routes stated; dosages and duration of treatments to reaction onset not stated]. The woman was diagnosed with RRMS in 2012, at the age of 35 years. She was treated with interferonbeta- 1a, which was discontinued later. In 2015, she started receiving dimethyl fumarate [Tecfidera] 120mg twice daily. In 2017, she presented with onset of double vision [aetiology not stated]. Brain MRI showed a gadolinium-enhancing lesion, however, not anatomically correlated with the symptoms. She was treated with methylprednisolone with resolution in symptoms. Thereafter, her dimethyl fumarate dosage was increased to 240mg twice daily. In 2019, she presented with right hand numbness with diminished dexterity and left lower extremity numbness. She started receiving IV methylprednisolone therapy. Later, she developed COVID-19 infection [aetiology not stated]. Thus, she discontinued dimethyl fumarate therapy for 1 month in July 2020 and continued thereafter. In January 2021, she started receiving the generic form of dimethyl fumarate. In July 2021 and August 2021, she received her tozinameran [Pfizer-BioNTech COVID-19 mRNA vaccine; BNT162b2] vaccination. In October 2021, she presented with subacute onset of right temple pain which progressed into jaw pain, associated with a few blisters located in the right lips corner. HZ was considered, which was secondary to dimethyl fumarate, methylprednisolone and tozinameran therapies. The woman started treatment with aciclovir [acyclovir] and prednisone. She presented to the emergency room due to HZ. Eventually, she was hospitalised and treated with aciclovir. After admission, generic form of dimethyl fumarate was discontinued. Lymphocytes subpopulations count after discontinuation showed lower proportions of CD8+ T cells and higher percentages of natural killer cells. She was discharged on aciclovir, with resolution in HZ. She was scheduled to receive zoster vaccine in 1 year. Few days later, she developed new low left lower extremity numbness and weakness along with urinary retention. MS exacerbation was diagnosed. Eventually, her dimethyl fumarate therapy was restarted along with valaciclovir [valacyclovir]. Few weeks later, elevation of the NK cells was observed, which was suspected to be HZ reactivation [aetiology not stated]. She was treated with methylprednisolone along with physical therapy with improvement in her condition. MS exacerbation was secondary to HZ. Amendment: This follow-up report is being submitted to allow appropriate reporting to FDA with the correct NDA. Follow-up (11Dec2025): This is a literature report, Program ID: for the following literature source(s): This is a follow-up report based on the receipt of the publication; the case has been updated to include additional information identified in the publication. Updated information: reporter, literature information, RMH, laboratory data, and product information (vaccination dosing; Comirnaty license updated). A 44-year-old woman with no reported history of chickenpox disease, chicken pox or zoster vaccination, was diagnosed with RRMS at age 35, in 2012. She received MS care outside the institution from disease onset till 2017 when she transferred her care over. Upon disease onset, she started treatment with interferon beta 1a, given intramuscularly at the dose of 30 ug once weekly. In 2015, due to injections fatigue, she started DMF at the dose of 120 mg twice daily. In Mar2017 she transferred her care to the institution where she presented with new onset of double vision since about 2 weeks. A brain magnetic resonance imagining (MRI) showed a gadolinium-enhancing lesion which was however not anatomically correlated with the symptoms. She received intravenous methylprednisolone (IVMP) with symptoms resolution. DMF was increased to 240 mg twice daily and she has remained on this dose ever since, tolerating it well. Both white blood cell (x10 3/uL; 2 years on DMF: 3.5 and 5.8; 3 years on DMF: 4.1 and 5.6; 4 years on DMF: 5.5 and 5.3; 5 years on DMF: 6.2 and 5.1; and 6 years on DMF: 5.8 and 6.7) and absolute lymphocyte counts (2 years on DMF: 1.43 and 1.92; 3 years on DMF: 1.44 and 2.11; 4 years on DMF: 1.87 and 1.64; 5 years on DMF: 1.84 and 1.88; and 6 years on DMF: 2.34 and 1.61) have persisted within normal limits. In 2019, she reported right hand numbness with diminished dexterity and left lower extremity numbness, requiring IVMP, although these symptoms lacked MRI correlates of gadolinium-enhancing lesions. In Jul2020, she remained off DMF for one month due to COVID-19 infection, featured by a mild flu-like syndrome. In Jan2021 she started receiving the generic form of DMF. In Jul2021 and Aug2021, she received the Pfizer-BioNTech COVID-19 mRNA vaccine (BNT162b2). After 6 years of DMF treatment (inclusive of both the brand and the generic forms), in Oct2021, she reported subacute onset of right temple pain which progressed into jaw pain, associated with a few blisters located in the right lips corner. She started oral acyclovir at a dose of 800 mg 5 times per day and prednisone. Five days after the occurrence of the facial pain and the use of oral acyclovir she presented to the emergency room of the institution due to spread of the blisters over the right cheek, with diffuse intense nerve pain along the right cheek and jaw. Due to failure to respond to oral antiviral treatment, the patient was admitted to the hospital and treated with IV acyclovir (10 mg/kg body weight) 3 times per day. At the time of admission, her absolute white blood cell and lymphocyte counts were within normal limits. DMF was discontinued. Lymphocytes' subpopulations count (WBC: 6.5 x10 3/uL, Lymphocyte proportion: 37.4%, absolute lymphocyte count: 2.43 x10 3/uL, CD3 proportion: 69%, CD3 absolute count: 1677/uL, CD8 proportion: 17%, CD8 absolute count: 413/uL, CD4 proportion: 51%, CD4 absolute count: 1239/uL, CD16&56 proportion: 15%, CD16&56 absolute count: 364/uL, CD19 proportion: 17%, CD19 absolute count: 413/uL) obtained five days upon admission and DMF discontinuation showed lower proportions of CD8 + T cells and higher percentages of natural killer (NK) cells. Notably, absolute values were within normal limits. Repeated brain, C- and T-spine MRI showed a new non-symptomatic gadolinium-enhancing lesion in the left temporal lobe compatible with active demyelination but otherwise no changes in the overall lesion burden relative to the time of start of 240 mg twice a day DMF, 6 years prior. The patient showed partial response within two days upon IV acyclovir and was discharged home on oral regimen, e.g., 800 mg acyclovir 5 times per day for 11 days. (2 months after admission: WBC: 5.7 x10 3/uL, Lymphocyte proportion: 36.4%, absolute lymphocyte count: 2.13 x10 3/uL, CD3 proportion: 63%, CD3 absolute count: 1342/uL, CD8 proportion: 16%, CD8 absolute count: 341/uL, CD4 proportion: 44%, CD4 absolute count: 937/uL, CD16&56 proportion: 24%, CD16&56 absolute count: 511/uL, CD19 proportion: 13%, CD19 absolute count: 277/uL.) Per discussion with the infectious disease specialist DMF was restarted once the rash resolved completely. She also started preventive treatment with valacyclovir at the dose of 500 mg twice a day for 6 months and will receive the zoster vaccine in one year from this event, provided that no additional HZ events will occur in between. Eight weeks later, absolute values of lymphocytes' subsets were within normal limits, except for some elevation of the NK cells, which the authors interpreted as secondary to the immune-protective reaction against the HZ reactivation. The cutaneous blisters, lesions and rash had resolved. Thus, DMF at the dose of 240 mg twice a day was restarted. A few days later, the patient developed new low left lower extremity numbness and weakness along with urinary retention. Repeated MRI showed a new gadolinium-enhancing lesion in the thoracic spine. She therefore received a 5-day course of IVMP in addition to physical therapy and has returned nearly to her baseline in a few weeks. Per discussion, the following aspects diversify our case from previous anectodical reports: (1) the site of cutaneous HZ reactivation, e.g., face, (2) the timing with respect to DMF start, e.g., 6 years, and (3) initial resistance to oral treatment with acyclovir. Furthermore, the occurrence of cutaneous HZ in the patient likely led to a new non-symptomatic active lesion which was the only new lesion counted on the patient's scan relative to the time of DMF start. This isolated radiological activity eventually progressed into a full clinical exacerbation a few weeks later, likely also because IVMP administration had to be initially deferred. Two additional considerations must be discussed to appropriately conceptualize the report. First, one may speculate that HZ infections may be an indicator of other occult opportunistic infections potentially becoming active during the prolonged use of DMF. While this is a valid speculation, it is important to note that a large study based on 1736 reported only < 1% occurrence of opportunistic infections with DMF. Second, one may argue that a multifactorial pressure on the immuno- logical system secondary to the COVID-19 infection in 2020 and subsequent vaccination about 10 weeks prior to the HZ occurrence, could have led to its reactivation. Both might have increased the demands of the lymphocyte population yielding to a normally quiescent virus to become active. At this time, this remains an intriguing but purely speculative inference. Amendment: This report was incorrectly submitted to the FDA with Biologic License Application number for BNT162B2 and is now being submitted with the correct Emergency Use Authorization number 027034 for BNT162B2. This is also being submitted to amend previously reported information: The narrative was updated to reflect that the previous follow-up information was received on 11Dec2025 (instead of 12Dec2025). Follow-up (22Dec2025): This is a follow-up report to notify that the case PV202300164051 and 202500251601 are duplicates. All subsequent follow-up information will be reported under manufacturer report number 202500251601.; Sender's Comments: Based on the limited information provided in this case, a contributory role of the suspect product BNT162b2 (COMIRNATY) to the reported event cannot be excluded. Event is considered Related conservatively. There is very limited information provided in this report. Case will be reassessed upon receipt of additional information.
Medical History/Concurrent Conditions: Relapsing-remitting multiple sclerosis (At the age of 35 years)
TECFIDERA
Test Name: CD19 absolute count; Result Unstructured Data: Test Result:413 /mm3; Test Name: CD19 absolute count; Result Unstructured Data: Test Result:277 /mm3; Test Name: CD19 proportion; Test Result: 17 %; Test Name: CD19 proportion; Test Result: 13 %; Test Name: CD3 absolute count; Result Unstructured Data: Test Result:1677 /mm3; Test Name: CD3 absolute count; Result Unstructured Data: Test Result:1342 /mm3; Test Name: CD3 proportion; Test Result: 69 %; Test Name: CD3 proportion; Test Result: 63 %; Test Name: CD4 proportion; Test Result: 51 %; Test Name: CD4 proportion; Test Result: 44 %; Test Name: CD4 absolute count; Result Unstructured Data: Test Result:1239 /mm3; Test Name: CD4 absolute count; Result Unstructured Data: Test Result:937 /mm3; Test Name: CD8 absolute count; Result Unstructured Data: Test Result:413 /mm3; Test Name: CD8 absolute count; Result Unstructured Data: Test Result:34 /mm3; Test Name: CD8 proportion; Test Result: 17 %; Test Name: CD8 proportion; Test Result: 16 %; Test Name: CD8+ T cells; Result Unstructured Data: Test Result:Lower proportions; Test Name: Absolute lymphocyte count; Result Unstructured Data: Test Result:1.43 x10 3/mm3; Test Name: Absolute lymphocyte count; Result Unstructured Data: Test Result:1.92 x10 3/mm3; Test Name: Absolute lymphocyte count; Result Unstructured Data: Test Result:1.44 x10 3/mm3; Test Name: Absolute lymphocyte count; Result Unstructured Data: Test Result:2.11 x10 3/mm3; Test Name: Absolute lymphocyte count; Result Unstructured Data: Test Result:1.87 x10 3/mm3; Test Name: Absolute lymphocyte count; Result Unstructured Data: Test Result:1.64 x10 3/mm3; Test Name: Absolute lymphocyte count; Result Unstructured Data: Test Result:1.84 x10 3/mm3; Test Name: Absolute lymphocyte count; Result Unstructured Data: Test Result:1.88 x10 3/mm3; Test Name: Absolute lymphocyte count; Result Unstructured Data: Test Result:2.34 x10 3/mm3; Test Name: Absolute lymphocyte count; Result Unstructured Data: Test Result:1.61 x10 3/mm3; Test Name: Absolute lymphocyte count; Result Unstructured Data: Test Result:2.43 x10 3/mm3; Test Name: Absolute lymphocyte count; Result Unstructured Data: Test Result:2.13 x10 3/mm3; Test Name: Lymphocyte proportion; Test Result: 37.4 %; Test Name: Lymphocyte proportion; Test Result: 36.4 %; Test Name: MRI; Result Unstructured Data: Test Result:New gadolinium-enhancing lesion; Comments: In the thoracic spine; Test Name: Brain MRI; Result Unstructured Data: Test Result:New non-symptomatic gadolinium-enhancing lesion; Comments: In the left temporal lobe compatible with active demyelination but otherwise no changes in the overall lesion burden; Test Date: 2017; Test Name: Brain MRI; Result Unstructured Data: Test Result:Gadolinium-enhancing lesion; Test Name: C- and T-spine MRI; Result Unstructured Data: Test Result:New non-symptomatic gadolinium-enhancing lesion; Comments: In the left temporal lobe compatible with active demyelination but otherwise no changes in the overall lesion burden; Test Name: CD16 and 56 absolute count; Result Unstructured Data: Test Result:364 /mm3; Test Name: CD16 and 56 absolute count; Result Unstructured Data: Test Result:511 /mm3; Test Name: CD16 and 56 proportion; Test Result: 15 %; Test Name: CD16 and 56 proportion; Test Result: 24 %; Test Name: NK cells; Result Unstructured Data: Test Result:Elevation; Comments: Higher percentages; Test Name: White blood cell absolute count; Result Unstructured Data: Test Result:3.5 x10 3/mm3; Test Name: White blood cell absolute count; Result Unstructured Data: Test Result:5.8 x10 3/mm3; Test Name: White blood cell absolute count; Result Unstructured Data: Test Result:4.1 x10 3/mm3; Test Name: White blood cell absolute count; Result Unstructured Data: Test Result:5.6 x10 3/mm3; Test Name: White blood cell absolute count; Result Unstructured Data: Test Result:5.5 x10 3/mm3; Test Name: White blood cell absolute count; Result Unstructured Data: Test Result:5.3 x10 3/mm3; Test Name: White blood cell absolute count; Result Unstructured Data: Test Result:6.2 x10 3/mm3; Test Name: White blood cell absolute count; Result Unstructured Data: Test Result:5.1 x10 3/mm3; Test Name: White blood cell absolute count; Result Unstructured Data: Test Result:5.8 x10 3/mm3; Test Name: White blood cell absolute count; Result Unstructured Data: Test Result:6.7 x10 3/mm3; Test Name: White blood cell absolute count; Result Unstructured Data: Test Result:6.5 x10 3/mm3; Test Name: White blood cell absolute count; Result Unstructured Data: Test Result:5.7 x10 3/mm3