Successful dupilumab treatment in bullous pemphigoid complicated with subacute hematogenous disseminated tuberculosis: A case report

Dear Editor, Subacute hematogenous disseminated tuberculosis (SHDT) is a serious infection commonly seen in the elderly, HIV-infected, and other immunosuppressed populations.1 Infections such as tuberculosis should be ruled out in Bullous Pemphigoid (BP) patients prior to systemic hormone therapy, while regular monitoring is still required during treatment.2 Here, we present a BP patient who experienced a recurrence and SHDT following 1 year of hormone therapy. A 72-year-old male patient presented 1 year ago with widespread erythema with tense blisters, negative Nikolsky signs, and intense pruritus. Pathological examination confirmed bullous pemphigoid (BP) (Figure 1A). Immunofluorescence testing showed C4(-), C1q(-), IgA(-), IgM(-), IgG(+), and C3(+-). Initial treatment included oral prednisolone acetate 60 mg, gradually tapered to 20 mg over 12 months, followed by self-discontinuation. Two months after discontinuation, the patient developed rapidly spreading erythema on the trunk and limbs, coalescing into patches with numerous cherry to walnut-sized translucent hemispherical bullae, severe pruritus, and several soybean-sized red superficial erosions on the oral mucosa. The affected skin was > 50% (Figure 2A). Pathological examination was consistent with bullous pemphigoid (Figure 1B). Prior to hormone therapy, the patient tested positive for T-spot (+) and PPD(++). Symptoms included high fever (max 39.5°C), breathlessness, and palpitations. Chest CT (Figure 1C) revealed bilateral small nodular infiltrates, suggestive of inflammatory lesions, and a right pneumothorax with bilateral pleural effusion. Bronchoscopy indicated potential old tubercular lesions, with a positive MTB tuberculosis complex group but negative acid-fast bacteria. Thoracic drainage yielded light yellow, blood-tinged fluid. Tuberculosis was not ruled out. The patient was diagnosed with subacute hematogenous disseminated tuberculosis (SHDT). Treatment included oral isoniazid (0.3 g/day), pyrazinamide (1 g/day), levofloxacin (0.6 g/day), and linzolid (600 mg/day). Concurrently, subcutaneous dupilumab (initial 600 mg, then 300 mg biweekly) was administered. Within a day, significant pruritus reduction was noted; by day 5, blisters resolved, and swelling decreased. Most skin rashes had resolved by the tenth day (Figure 2B), and he was discharged rash-free. After six injections, the skin was clear except for residual pigmentation (Figure 2C). Due to financial constraints, the patient switched to oral glucocorticoids (methylprednisolone 20 mg/day), with no skin lesion recurrence after 2 months. SHDT, which lacks specificity in both imaging and clinical presentation, is difficult to diagnose.1 It can be exacerbated by immune suppression, such as in systemic hormone therapy or HIV infection.1 The pathogenesis of SHDT may involve T-cell exhaustion. In immunocompromised patients, metabolic reprogramming and mitochondrial dysfunction lead to hematogenous dissemination of Mycobacterium tuberculosis.3 Dupilumab is an IL-4Rα antagonist that inhibits Th2 inflammatory responses, providing significant short-term improvement in refractory BP and demonstrating high safety in long-term maintenance therapy.2, 4 Dupilumab has been reported to treat refractory pemphigus vulgaris (PV) patients combined with episodic pulmonary tuberculosis and to treat pulmonary tuberculosis patients combined with vesicular pemphigoid under 3 months of systemic treatment.5, 6 In this case, the patient's BP and tuberculosis were effectively managed with dupilumab and standard tuberculosis therapy, without adverse reactions or tuberculosis recurrence over 9 months. This case is possibly the first to report successful dupilumab use in BP with SHDT. While promising, more clinical cases are required to investigate this treatment effectively. The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. The authors declare no conflicts of interest. This study has been approved by the patient. The data underlying this article will be shared on reasonable request to the corresponding author.