Pemphigoid or Psoriasis? 65-Year-Old's Remote Diagnosis Race

Medscape

5 days ago

Patients with cancer often require specialised care at centres located far from their residence. During the COVID-19 pandemic, telemedicine has rapidly gained ground as a way to ease system pressures and maintain continuity of care.
A 65-year-old man developed severe cutaneous toxicity, presenting as a rare bullous pemphigoid (BP) rash after 2 years on nivolumab. Notably, the reaction occurred in an outpatient setting during the COVID-19 pandemic. With coordinated support from rural providers and the use of telemedicine, his corticosteroid-refractory immune checkpoint inhibitor (ICI) toxicity was successfully managed.
The case reported by Tom Marco, DO, and colleagues from the Department of Internal Medicine, University of Arizona College of Medicine, Tucson, Arizona, highlighted how remote monitoring helped diagnose and manage a rare but serious complication of cancer therapy.
The Patient and His History
The patient with no prior medical history presented to the emergency department with gross haematuria. A CT scan of the abdomen and pelvis revealed a large right renal mass, embracing the inferior margin of the liver without renal vein involvement or capsular extension. A CT of the chest corroborated no definite metastasis to other organs or lymph nodes. Because there was no evidence of distant metastatic disease on imaging, a right radical nephrectomy with adrenalectomy was performed by urology, without complications. The pathology report was notable for clear cell renal carcinoma.
Because the patient came from a rural area, the examinations took place at a centre 3 hours away from his place of residence. The patient was subsequently examined by medical oncology, which calculated the probability of early disease progression to be low, with a recurrence rate of 8.4%. Given the low risk for recurrence, no adjuvant systemic therapy was recommended. The patient continued follow-up with medical oncology and remained under surveillance with CT scans every few months.
Findings and Diagnosis
At 24 months, a new right upper lobe (RUL) pulmonary nodule measuring 6 mm was found on chest CT. The nodule size was considered nonpathologic. Furthermore, the lesion was not feasible for biopsy, and the patient continued to be under close surveillance.
By month 36, the RUL pulmonary nodule measured 10 mm. A new left upper lobe nodule measuring 6 mm and a new right lower lobe lesion measuring 2 mm were discovered. A follow-up PET scan showed nonavid nodules, and biopsy was not feasible.
At 48 months, lesion progression prompted biopsy, which confirmed metastatic recurrence of renal cell carcinoma (RCC). The cancer was staged as IV (pT2cN0cM1).
First-line treatment with nivolumab and cabozantinib was initiated.
Cycles 2-5: The patient experienced mild fatigue, a grade 1 skin rash, gastrointestinal symptoms, and a 4 kg weight loss.
Cycle 9: Weight loss exceeding 10% of body weight prompted cabozantinib dose reduction.
Cycle 13: The patient developed diffuse skin changes, including blisters and open lesions, which led to cabozantinib discontinuation.
Cycle 14: Despite stopping the TKI, he developed severe blistering skin reactions involving more than 30% of the body surface area. ICI therapy was paused, and high-dose corticosteroids were initiated.
Skin biopsy confirmed BP, a rare autoimmune blistering disorder. The patient was treated with systemic corticosteroids, high-potency topical steroids, and doxycycline. Due to the limited response, rituximab was introduced for corticosteroid-refractory disease. After four doses, marked clinical improvement was observed: The skin lesions regressed, and no new blisters developed.
By day 172, the patient was free of skin symptoms. Given the absence of active disease and the severity of prior toxicity, a surveillance protocol was adopted.
Discussion
BP is a rare but potentially life-threatening immune-related adverse event (irAE) associated with ICI therapy. Early recognition and prompt, aggressive management, including biologic agents such as rituximab, are essential to ensure optimal outcomes.
The combination of ICI with TKI has become the standard therapeutic approach for the initial management of advanced RCC due to decreased mortality and increased long-term survival rates. Although this combination of medications has positively affected RCC treatment, the side effects can be severe.
In this case report, it was initially suspected that cabozantinib caused cutaneous manifestations and gastrointestinal adverse effects. In numerous studies, more than 70% of patients taking cabozantinib developed one or more cutaneous toxicities, including erythema, hand-foot skin reactions with or without blisters, pruritus, seborrheic dermatitis, stomatitis, and xerosis.
Alternatively, cutaneous manifestations with nivolumab have been reported in approximately 34% of patients or fewer and include maculopapular rash, eczema, lichenoid rashes, vitiligo, pruritus, and rarely, bullous eruptions.
Although the dose of cabozantinib was initially reduced and eventually stopped due to multiple suspected toxicities, the patient developed a new, rapidly progressing corticosteroid-refractory rash that continued to worsen to grade 4 toxicities. The pathology was characteristic of extremely rare BP ICI toxicity. Consequently, the decision to discontinue nivolumab therapy was made. Despite discontinuation of the offending agent, his BP began to improve only after the initiation of rituximab in combination with corticosteroids. This suggests that the cutaneous toxicity was attributable to nivolumab, indicating that it was an ICI-related adverse effect.
The mechanisms underlying irAEs are not fully understood. Multiple theories have been proposed, including a pro-inflammatory state, uncontrolled activity of T cells, enhanced immune activation and response, and cytokine release. Skin irAEs are the most common, encompassing 17%-40% of toxicities.
This case highlights the complex care challenges faced by rural patients with cancer. The patient resided more than 3 hours from the nearest specialised oncology centre, an access barrier further compounded by the COVID-19 pandemic. With less than 7% of oncologists available in rural areas, there is a significant gap in care.
The patient was able to receive cancer treatment, undergo detailed toxicity monitoring, and benefit from multidisciplinary input without a significant travel burden. Early detection and management of high-grade toxicities through remote assessments and coordinated care enabled successful treatment outcomes. Given this, structured telehealth surveillance protocols are crucial and can effectively serve rural areas that lack specialty centres.