Development of Bullous Pemphigoid in a Patient With Psoriasis and Metabolic Syndrome

Comment

Psoriasis Comorbidities

The correlation between PV and cardiovascular disorders such as myocardial infarction, cerebrovascular accident, and pulmonary embolism has been well established and is widely accepted.² It also has been documented that the risk for metabolic syndrome with components such as diabetes mellitus, hypertension, lipid abnormalities, obesity, and arteriosclerosis is notably increased in PV patients.⁶ Moreover, associated internal disorders are responsible for a 3- to 4-year reduction in life expectancy in patients with moderate to severe PV.⁷

Correlation of PV and BP

Psoriasis also may coexist with autoimmune disorders such as rheumatoid arthritis, lupus erythematosus, and blistering disorders.⁸ There are more than 60 known cases reporting PV in association with various types of subepidermal blistering diseases, including pemphigus vulgaris, epidermolysis bullosa acquisita, anti-p200 pemphigoid, and BP.^8,9 The pathogenetic relationship between BP and PV remains obscure. In most published cases, PV preceded BP by 5 to 30 years, possibly ascribable to patients being diagnosed with PV at a younger age.⁹ In general, patients with BP and PV are younger than patients with BP only, with a mean age of 62 years.⁹ Because our patient was in his mid-30s when he developed BP, in such cases physicians should take under consideration any triggering factors (eg, drugs). Physical examination and detailed laboratory findings allowed us to make the patient aware of the potential for development of metabolic syndrome. This condition in combination with PV could be a predisposing factor for BP development. According to more recent research, PV is considered a generalized inflammatory process rather than a disorder limited to the skin and joints.¹⁰ The chronic inflammatory process in psoriatic skin results in exposure of autoantigens, leading to an immune response and the production of BP antibodies. The neutrophil elastase enzyme present in psoriatic lesions also may take part in dermoepidermal junction degradation and blister formation of BP.¹¹ According to other observations, some antipsoriatic therapies (eg, psoralen plus UVA, UVB, dithranol, coal tar) could be associated with development of BP.¹² Moreover, it was shown that psoralen plus UVA therapy, which is widely used in PV treatment, alters the cytokine profile from helper T cells T_H1 to T_H2.¹² T_H2-dependent cytokines predominate the sera and erosions in BP patients and seem to be notably relevant to the pathophysiology of the disease.¹³ The history of our patient’s psoriatic treatment included only topical corticosteroids, keratolytic agents, and occasionally dithranol and coal tar; however, UV phototherapy or any other systemic therapies had never been utilized. Three previously reported cases of patients with PV and BP also revealed no history of UV phototherapy,^8,9 which suggests that mechanisms responsible for coexistence of PV and BP are more complex. It has been proven that proinflammatory cytokines secreted by T_H1 and T_H17 cells, in particular tumor necrosis factor α, IL-17, IL-22, and IL-23, play an important role in the development of psoriatic lesions.¹⁰ On the other hand, these cytokines are known to contribute to vascular inflammation, leading to development of arteriosclerosis, as well as to regulate adipogenesis and obesity.^14,15 Arakawa et al¹⁶ reported increased expression of IL-17 in lesional skin in BP. They concluded that IL-17 may contribute to the recruitment of eosinophils and neutrophils and tissue damage in BP. Therefore, it is highly likely that IL-17 might be a common factor underlying the coexistence of BP with PV and metabolic syndrome. More such reports are required for better understanding this association.

BP Treatment

Selecting a therapy for BP with coexistent PV is challenging, especially in patients with extreme obesity and metabolic syndrome. It is well established that obesity correlates with a higher incidence of PV and more severe disease. On the other hand, obesity also influences response to therapy. Systemic corticosteroids are contraindicated in psoriasis patients because of severe side effects, such as rebound phenomenon of psoriatic lesions and risk for development of generalized pustular PV. Although systemic corticosteroids are effective in BP, high-dose therapy may potentially be life-threatening, particularly in these obese patients with conditions such as hypertension and diabetes mellitus, among others,¹ as was observed in our case. Taking into consideration the above mentioned conditions and our experience on such cases, the current patient had received MTX (12.5 mg once weekly) and clobetasol propionate cream, which led to the rapid healing of the psoriatic plaques, whereas BP was more resistant to this therapy. This response may be explained by our patient’s class 3 obesity (body mass index, 69.2). Therefore, the dose of MTX was increased to 20 mg once weekly and was successful. The decision to use MTX was supported by evidence that this medicine may reduce the risk for arteriosclerosis and cardiovascular disorders.¹⁷

There are some alternative therapeutic options for patients with coexisting BP and PV, such as cyclosporine,¹⁸ combination low-dose cyclosporine and low-dose systemic corticosteroids,¹⁹ dapsone,²⁰ azathioprine,²¹ mycophenolate mofetil,²² and acitretin.²³ It also has been shown that biologics (eg, ustekinumab) may be a successful solution in patients with PV and antilaminin-γ1 pemphigoid.²⁴ However, these alternative therapeutic regimens could not be considered in our patient because of serious coexisting internal disorders.