Spot the Itchy Elderly Patient: Bullous Pemphigoid as a Continuum
In this special conference coverage from RAPIDS 2026 in Fort Lauderdale, host PA Eileen Cheever sits down with Dr. Naiem Issa to unpack the two lectures he delivered on autoimmune blistering disease. Dr. Issa's number one lesson on bullous pemphigoid (BP) is simple: keep it high on your differential for the itchy elderly patient who walks through the door.
He stresses that BP is a continuum. It may start as itch, progress to urticarial plaques and patches that can look like eczema, and only later produce the tense bullae seen in textbooks. Because the patient may or may not have skin findings in the moment, clinicians must recognize different morphologies rather than wait for the classic blister.
Dr. Issa also insists on a proper medication reconciliation. About half the time, he notes, BP can be medication-induced, so that history is essential before weighing whether to stop a suspected offending drug. For the de novo cases, he still works up other causes of itch in the elderly, including atopic dermatitis and malignancy.
Biopsy Technique and Serology in BP
Dr. Issa walks Cheever through the difference between H&E histology and DIF (direct immunofluorescence). For histology, he recommends a standard punch biopsy deep enough to reach from the stratum corneum to the dermis, or even subcutaneous tissue. Critically, when biopsying a bulla, sample the edge of the lesion — biopsy directly into the bulla, and you risk losing the top of the epidermis and, with it, the diagnosis.
For DIF, the sample comes from the perilesional area, within one centimeter of the lesion. As Dr. Issa explains, that's where the autoantibodies gather along the basement membrane zone before the lesion actually splits — IgG, IgA, or IgM lining the dermal-epidermal junction. Cheever calls out how helpful it is to understand why we go perilesional, not just that we do.
On serology, Dr. Issa uses BP-180 and BP-230, IgG autoantigens that target the basement membrane. Because studies show these levels wax and wane with disease activity, he leans on them to assess where a patient sits from an inflammatory standpoint.
Type 2 Inflammation and a New Therapeutic Avenue
Dr. Issa ties the pathophysiology back to the B cells that produce the autoantibodies. Those B cells are reactive to IL-4 and IL-13 and carry an IL-4 receptor — the entry point for type 2 inflammation. When IL-4 and IL-13 bind the IL-4 receptor, the B cells produce autoantibodies, typically IgG but also IgE, IgM, and IgA.
This explains why you see IgG on DIF even though routine DIF doesn’t look for IgE. It also points to why blocking type 2 inflammation matters. Dr. Issa notes an FDA-approved option—dupilumab—to stop the type 2 inflammation driving autoantibody generation in BP.
Pemphigus: Desmogleins, Presentations, and Emerging Signaling
Turning to his second lecture, Dr. Issa contrasts pemphigus with BP. In pemphigus vulgaris, autoantibodies target desmogleins (and possibly desmocollins) that link keratinocytes in the brick-and-mortar architecture higher up toward the stratum corneum. That superficial location produces flaccid blisters, unlike the tense bullae of BP.
He describes the mix-and-match of desmoglein 1 and 3 involvement: classic pemphigus vulgaris affects both, with mucous membrane and skin disease, while desmoglein 1 alone trends toward the more superficial foliaceus. But the marriage isn't always perfect — some patients land in an overlap 'no man's land,' so Dr. Issa reminds clinicians to treat the patient in front of them, not just the antibody panel.
On pathophysiology, he flags novel data: autoantibody binding to desmogleins and desmocollins involves JAK-STAT signaling, and one study showed topical JAK1/JAK2 inhibition led to resolution of pemphigus vulgaris skin. Blocking that downstream pathway may prevent keratinocyte destruction. Diagnostically, DIF shows the characteristic 'chicken wire' pattern of IgG and IgA in the epidermis, distinct from the fluorescent green basement membrane of BP, and serology for anti-DSG antibodies is a useful adjunct, especially when DIF is negative or the picture is in that middle ground.
Pemphigus Emergencies and Therapy
Dr. Issa doesn't sugarcoat how sick pemphigus vulgaris patients can be. With significant body surface area involved, they behave like burn patients — transepidermal water loss, fluid and electrolyte imbalance, and high infection risk from broken skin and altered immunity. These are emergent presentations that need prompt treatment or ER referral.
He also raises mucocutaneous and esophageal involvement, where difficulty eating drives weight loss and protein imbalance, plus strictures of the esophagus, urinary tract, or anal canal that warrant the respective specialists for dilation.
For therapy, Dr. Issa frames it conceptually: it's an inflammatory condition with autoantibodies, so stop the source. Rituximab (anti-CD20) to deplete B cells is the current standard of care in pemphigus. He points to dupilumab to stop type 2 inflammation (established in BP; remains to be seen in pemphigus) and to Bruton tyrosine kinase (BTK) inhibitors as a promising but not yet FDA-approved target. When in doubt, he notes, corticosteroids and immunomodulators like cyclosporine or mycophenolate mofetil address the underlying pro-inflammatory state.