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CORRESPONDENCE
Year : 2022 | Volume
: 40
| Issue : 4 | Page : 237-238
Refractory bullous pemphigoid with prurigo nodularis successfully treated with dupilumab monotherapy
Po-Ta Lai1, Han-Chi Tseng2
1 Department of Dermatology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan
2 Department of Dermatology, Kaohsiung Chang-Gung Memorial Hospital; College of Medicine, Chang Gung University, Kaohsiung, Taiwan
Correspondence Address:
Dr. Han-Chi Tseng
Department of Dermatology, Kaohsiung Chang-Gung Memorial Hospital, No. 123, Dapi Road., Niaosong Dist., Kaohsiung City 833401
Taiwan
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/1027-8117.357999
Dear Editor,
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disorder. The autoantibodies against BP180 and BP230, which are indispensable for basement membrane zone integrity. Its classical presentation includes multiple tense bullae. Elevated interleukin (IL)-4 and IL-13 levels were recently detected in the blood and blister fluids of affected patients.[1] Dupilumab, an IL-4Rα antagonist, inhibits Th2-mediated inflammation. Dupilumab is approved for managing atopic dermatitis and chronic rhinosinusitis with nasal polyposis; it has also been successfully used off-label to treat pruritic dermatoses. A recent report revealed the beneficial outcomes of dupilumab in refractory BP.[2]
An 86-year-old male with Type 2 diabetes mellitus, chronic kidney disease, and triple-vessel coronary artery disease presented at our telemedicine clinic with a 3-month history of multiple, discrete pruritus on his back. He used gliclazide, pioglitazone, linagliptin, acarbose, and insulin for diabetes mellitus since diagnosed in 2013. According to him, biannual bullous attacks occurred since 2011. A skin biopsy in 2017 showed subepidermal blisters containing eosinophils, lymphocytes, and neutrophils. Direct immunofluorescence showed linear immunoglobulin G (IgG) and C3 deposition along the basement membrane zone confirming the diagnosis of BP. A physical examination revealed multiple, discrete prurigo nodularis (PN) lesions on the scalp, chest, and back. [Figure 1]a. He complained of extreme pruritus and sleep disturbances. However, no blisters or rashes were observed.
Figure 1: (a) The initial presentation of skin lesions before the initiation of dupilumab for the patient's PN. There were multiple erythematous, large, protruding nodules with erosions on the back. (b) The picture showed bullous pemphigoid with PN. There were some tense bullae with some flattened erythematous nodules on his back with excoriation. (c) The picture revealed the resolution of previous PN and bullous pemphigoid with persistent hyperpigmentation after 6 months of dupilumab therapy. PN: Prurigo nodularis.The patient took azathioprine 50 mg daily for 2 months. Partial clinical improvement was observed, but the azathioprine was discontinued because of leukopenia 2 months into the therapy. Next, we administered dupilumab (loading dose, 600 mg; 300 mg every other week) as monotherapy for PN. Almost all of the PN flattened rapidly within 2 months. However, multiple blisters on the trunk and limbs [Figure 1]b appeared 2 weeks after the first injection of the AstraZeneca COVID-19 vaccine. The DPP-4 inhibitor was stopped after the bullous attack. Systemic steroid treatment (methylprednisolone 4–32 mg/day), doxycycline (100 mg twice daily), topical clobetasol 0.05 ointment, and systemic antihistamines were administered as adjuvant therapy in addition to the dupilumab. The generalized blisters gradually subsided after another 2 months of treatment with dupilumab [Figure 1]c. Since then, dupilumab monotherapy has been used. The patient reported nearly complete resolution of the pruritus, and he remained free of blisters and PN for 10 months after dupilumab monotherapy. However, when we attempted to prolong the dosing interval to every 3 weeks, the bullous lesions recurred. Therefore, he received dupilumab 300 mg every other week as a monotherapy.
Choosing a proper therapeutic regimen for patients with extensive and recalcitrant BP can be challenging because most patients are senile and combined with multiple chronic diseases. The initial dosage of an oral steroid in patients with extensive BP, typically lower than 0.75 mg/kg/day, usually leads to rapid disease control within 1 month.[3] However, long-term therapy with systemic corticosteroids is limited because of adverse effects, including hyperglycemia, hypertension, cataracts, osteoporosis, and unmentioned, immunosuppressive effects. Besides, refractory pruritus in the elders may be associated with the senile type of atopy, which could be a prodrome of BP.[4] Dupilumab, a fully human monoclonal IgG4 antibody that inhibits the major Th2 cytokines IL-4 and IL-13 by targeting the interleukin-4 receptor,[1],[5] provided as a safe steroid-sparing agent[2] Moreover, dupilumab can indirectly decrease the secretion of IgE and eosinophil activity[6] and manage these elevated biomarkers in BP patients through multiple mechanisms, including the downregulation of eosinophil and helper T-cell Type 2-associated chemokine activity.[7] Furthermore, dupilumab can address pruritus by directly inhibiting IL-4 and IL-13 and decreasing IL-31 by affecting eosinophils.[8]
Here, we presented a rare case of an elderly man with PN, BP, and multiple chronic diseases, which created great treatment challenges. We initially administered dupilumab to control the PN, which showed a rapid and satisfactory response. The pruritus was rapidly relieved 1 week after the loading dose. However, the treatment effect on the BP was relatively slower, as it took nearly 2 months to show desirable effects. We cannot exclude the possibility that the acute exacerbation of BP was triggered by the AZ vaccine, which may require further clarification in the future.
Our patient tolerated the dupilumab well without any adverse effects. The case we presented here suggests that dupilumab could be an effective and safe alternative treatment for BP with PN that cannot be completely controlled by traditional regimens. This successful treatment experience with dupilumab also implicates that Th2 skewing senile atopy and BP may be concomitant. Further studies are needed to determine the optimal dupilumab dose and efficacy for both diseases.
Declaration of patient consent
The authors certify that they have obtained appropriate patient consent form. In the form, the patient has given his consent for the images and other clinical information to be reported in the journal. The patient understands that his name and initial will not be published and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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