Keloidal scarring in pemphigus: A report of two cases

Dear Editor,

Pemphigus vulgaris (PV) is an uncommon autoimmune blistering disease characterised by intra-epidermal blistering due to formation of autoantibodies against desmogleins. Although it traditionally heals without scarring, emerging evidence and case reports suggest an association with hypertrophic or keloidal scarring. Shared Th2-mediated immune pathways may underlie both conditions, with dupilumab showing promise in treating them. Keloidal scarring, which is characterized by excessive collagen deposition, is an uncommon and poorly understood phenomena in PV patients. Skin diseases associated with keloidogenesis include acne vulgaris, hidradenitis suppurativa and severe type 2 reaction in leprosy, among others.

A 32-year-old Asian woman, diagnosed case of PV, presented with multiple keloidal lesions on the breasts, abdomen, both arms and the dorsum of right foot for the last one month [Figures 1a-d]. There was presence of post-inflammatory hyperpigmentation in surrounding areas, suggestive of healing lesions of pemphigus. The patient had received two injections of rituximab, 1gram infusion each, two weeks apart (rheumatoid arthritis protocol) in the past, received tapering doses of prednisolone after achieving end of consolidation that was eventually stopped before presenting to us.

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Figure 1: a) Index case of a 32-year-old woman, diagnosed case of pemphigus vulgaris with multiple keloids on the dorsum of right foot b) Keloids on breasts c) Keloids on left arm d) Surrounding areas show post-inflammatory hyperpigmentation.

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In another 45-year-old Asian female, similar keloidal lesions appeared on the breasts after healing of blisters. These keloidal lesions were preceded by blisters at the same site [Figure 2].

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Figure 2: A 45-year-old woman with keloidal lesions on the breasts. These were preceded by blisters at the same site.

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There was no family history of keloid formation and neither of the two patients had any past history of keloidal scarring. A biopsy was not performed given the classic presentation of the keloids; clinical diagnosis was made. Both patients were treated with silicone gel sheets and intralesional triamcinolone 40mg/mL, every four weeks to which they responded evidenced by a decrease in the size of the keloidal lesions.

Inflammatory mediators, wound tension and genetic predisposition are some of the factors that contribute to keloid formation, a phenomenon that is less described in patients of PV because they are intraepidermal, vesicles and bullae in pemphigus heal without leaving scars unless there has been a secondary bacterial infection.¹ There might also be the role of chronic inflammation, cytokine dysregulation (e.g., tumour necrosis factor-α, interleukin-6), aberrant wound healing pathways and possible effects of tissue damage due to blistering on fibroblast activation.² In a case report of PV by Gupta et al., bullous lesions healed with minor keloidal scars and the lesions of PV had not been secondarily infected.³ Another hypothesis is the intricate communication between keratinocytes and underlying fibroblasts, impacted by apoptosis and acantholysis. Fibroblast dysregulation may be facilitated by dermal apoptotic cells and elevated levels of tumour necrosis factor-α, which could lead to keloids in vulnerable individuals.² Shivaswamy et al. described extensive keloids following cyclosporin therapy in a PV patient.⁴ Previously reported cases of keloid formation in immunobullous disorders have been summarised in Table 1.^1-7

Systemic corticosteroids which form the mainstay of therapy in PV, have been demonstrated to suppress collagen synthesis by blocking the activity of enzymes involved in collagen formation, as seen in in-vitro studies in a culture of fibroblasts. Additionally, steroids prevent glycosaminoglycans from forming. However, in both of our patients, keloids developed while they were being treated with prednisolone. The first patient was on prednisolone 5mg once a day and had been on tapering doses of prednisolone for the past 3 months, while the second patient was on 10mg once a day for the past 2 months when the keloids started developing. It is possible that the high dosage of prednisone prevented the development of keloid until it was reduced to 10 mg a day.

In uncommon circumstances, keloids can develop after a trivial trauma such as insect bite, tattoos and vaccinations. Pemphigus being an intraepidermal disorder does not usually cause scarring. Prolonged inflammation brought by ongoing epidermal injury might make patients more susceptible to aberrant scar formation. By encouraging fibroblast proliferation, collagen deposition and aberrant extracellular matrix remodelling, inflammation plays a critical role in keloid pathogenesis. Continuous blistering and healing cycles in PV may result in dysregulated repair pathways, which can increase the risk of keloid formation. The management of scarring and the underlying autoimmune disease should be the main goals of treatment for keloidal scars in PV. Large, symptomatic keloids may occasionally be surgically excised, though there is a chance of recurrence.

In conclusion, while keloidal scarring is uncommon in PV, its occurrence may be related to chronic inflammation, altered wound healing and the impact of long-term immunosuppressive treatment. Both keloids and PV involve dysregulated wound healing, tissue repair and immune responses. While systemic corticosteroids are typically known to suppress collagen synthesis, keloids can still develop while the patient is on steroids. There is also importance of managing these coexisting conditions together, especially in skin of colour, where keloid formation is more common. Clinicians managing PV should be aware of this potential complication.