Development of Chancre-Variant Cutaneous Tuberculosis After BCG Vaccine Administration in a Patient With Migraines

The BCG vaccine prevents acute forms of childhood tuberculosis (TB). It has been demonstrated that the vaccine enhances tumor necrosis factor alpha and interleukin-6 production by macrophages via nucleotide-binding oligomerization receptor signaling.^1,2 Consequently, this immunogenic response has been leveraged in the management of other medical conditions.³ For example, this nonspecific effect was suggested to train the innate immune system, and thereby ameliorate symptoms of SARS-CoV-2 infection^4-6 and treat superficial bladder cancer.^7-9 In the management of fibromyalgia, use of BCG vaccine is purported to improve symptoms by inducing a cytokine response.¹⁰

Tuberculous chancre occurs with direct inoculation of Mycobacterium bovis to the skin after local trauma. It is exceedingly rare, especially in adults, with previous research reporting that it accounts for only 1% to 2% of cutaneous TB.¹¹ In this report, the authors described a case of chancre-variant cutaneous TB that occurred in an adult following BCG vaccination.

Initial evaluation
A 73-year-old female with a history of fibromyalgia presented with an ulcer of the right upper extremity that had been present for 3 months (Figure 1). The patient reported that the ulcer directly overlaid the BCG vaccination site; the vaccine was administered for fibromyalgia treatment. Skin biopsy from an outside clinic showed granulomatous dermatitis and positive staining for M bovis; a culture had failed to grow any organism. The patient had no history of immunosuppression and was not receiving immunomodulating therapy. On physical examination, the patient was well appearing and afebrile. A large, nontender, full-thickness ulcer with a hypertrophic base was present on the proximal right arm.

Pathology
Initial biopsy at the authors’ institution revealed pseudoepitheliomatous epidermal and follicular infundibular hyperplasia with inflamed granulation tissue and confluent granulomatous infiltrates. Ziehl-Neelsen staining demonstrated numerous acid-fast bacilli (AFB) scattered throughout the granulomatous dermal infiltrate.

The hypertrophic wound base was subsequently debulked, and a fluorescent smear of the tissue showed AFB (Figure 2). Tissue culture showed AFB after 3 weeks of growth. Tissue smear demonstrated 2 AFB to 18 AFB per 50 fields, and 12 colonies with a rough and buff appearance were recovered from Löwenstein-Jensen slant in week 6 of incubation. A nucleic acid amplification test detected ribosomal RNA of mycobacterium TB complex. This constellation of findings was consistent with localized M bovis infection.

Follow-up evaluation
After surgical debulking, the patient was instructed to clean the wound base with saline every other day, pat it dry, and cover the area with an adhesive foam dressing. The patient was also started on isoniazid monotherapy 300 mg twice weekly. After 6 months of treatment, the wound was nearly healed (Figure 3).

Approximately 95% of pediatric patients who receive the BCG vaccine should expect a localized skin reaction at the injection site. Mild adverse events (AEs) expected in vaccine recipients include papule development at the injection site, which may later ulcerate, and swelling of the ipsilateral regional lymph nodes. Severe AEs are more extensive and include local subcutaneous abscesses, tuberculous chancre, lupus vulgaris, scrofuloderma, papulonecrotic tuberculids, and suppurative lymphadenitis.¹² Although AEs in pediatric populations have been well described, those in adult patients have not, especially those in adults with chronic illness.

As the BCG vaccine continues to gain popularity in the United States as an off-label therapy for other medical conditions, AEs in the adult population may increase in prevalence. Therefore, clinicians should be aware of this vaccine’s more serious side effects and how to recognize them. This case report highlighted a potential AE associated with BCG vaccination in an adult patient with chronic illness and a proposed method of treatment for this AE.

Questions remain about the unique risk associated with administration of BCG vaccine in adult patients with chronic illness. Because the BCG vaccine is proposed to manage other diseases, such as diabetes mellitus¹³ and multiple sclerosis,^3,14 randomized controlled trials are needed to further investigate the efficacy, rate, and severity of AEs in these vulnerable populations.

Herein is presented a case of an adult patient who received the BCG vaccine in an attempt to manage chronic migraines secondary to fibromyalgia. Even though the patient had no prior history of immunosuppression, chancre-variant cutaneous TB developed in response to the vaccination. Biopsy, stain, tissue culture, and nucleic acid amplification test all confirmed M bovis infection. The hypertrophic tumor was debulked, and a 6-month course of isoniazid monotherapy was initiated. In the interim, the patient was advised to cleanse the wound base with saline every other day, pat it dry, and cover the area with an adhesive foam pad.

As the BCG vaccine becomes more popular as a potential method for managing autoimmune and inflammatory disorders in the United States, it is important that clinicians be aware of the potentially severe side effects of the vaccine. The chancre variant of cutaneous TB is uncommon in adult populations but may rise in prevalence over time with increased use of the BCG vaccine as an off-label therapy for other medical conditions. Future research should focus on improving the quality of the vaccine, discovering management options for those in whom adverse reactions developed, and further characterizing severe dermatologic reactions that may manifest from the vaccine.

Authors: Scott Stratman, BS; Julio Diaz-Perez, MD; Paolo Romanelli, MD; and Hadar Lev-Tov, MD, MAS

Affiliation: Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL

Disclosure: The authors disclose no financial or other conflicts of interest.

ORCID: Hadar Lev-Tov, 0000-0001-6223-7001

Correspondence: Hadar Lev-Tov, MD, MAS, 1600 NW 10th Ave RMSB 2023, Miami, FL, 33136; hlevtov@med.miami.edu