Vasculitis and panniculitis associated with vemurafenib

Novoa, Roberto A.; Honda, Kord; Koon, Henry; Gerstenblith, Meg R.

doi:10.1016/j.jaad.2012.05.019

Cited by 22 publications

(27 citation statements)

References 4 publications

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“…The clinical presentation of the lesions was similar to other reported cases, with predominance in upper and lower extremities [3, 4, 5, 6, 7, 8, 9, 10]. Like our patient, almost all patients developed arthralgia [3, 4, 5, 6, 7, 8, 9, 10]. Histopathological examination in previous cases outlined lobular, septal, or mixed (both lobular and septal) panniculitis, in one case associated with vasculitis [3].…”

Section: Discussionsupporting

confidence: 84%

“…Cutaneous adverse effects are significantly reduced with BRAFi and MEKi association including photosensitivity (15% of patients, coBRIM), hand-foot syndrome (6% COMBI-d), hyperkeratosis (6% COMBI-d; 29% coBRIM), alopecia (5% COMBI-d; 30% coBRIM), skin papillomas (1% COMBI-d), keratoacanthomas (8% coBRIM), and squamous-cell carcinomas (11% coBRIM) [1, 2, 3]. While panniculitis has exceptionally been reported with BRAFi, to the best of our knowledge, this rare side effect has never been described with the use of MEKi [4, 5, 6, 7, 8, 9, 10]. Here, we report a patient who developed panniculitis after initiation of combined therapy for metastatic melanoma.…”

Section: Introductionmentioning

confidence: 99%

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Panniculitis Associated with MEK Inhibitor Therapy: An Uncommon Adverse Effect

Negulescu¹,

Deilhes²,

Sibaud³

et al. 2017

Case Rep Dermatol

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The combination of MEK inhibitor (cobimetinib, trametinib) and BRAF inhibitor (vemurafenib, dabrafenib) is now the first-line treatment in patients with BRAF V600-mutated metastatic melanoma. This association reduces cutaneous adverse events induced by BRAF inhibitors alone, including photosensitivity, hand-foot syndrome, hyperkeratosis, alopecia, skin papillomas, keratoacanthomas, and squamous-cell carcinomas. While panniculitis has exceptionally been reported with BRAF inhibitors, this rare side effect has never been described with the use of MEK inhibitors. We present here the first observation of panniculitis strictly induced by MEK inhibitors. Indeed, 10 days after the initiation of combined treatment with cobimetinib and vemurafenib for metastatic melanoma, our patient developed panniculitis predominantly on the upper and lower extremities. These cutaneous nodules disappeared during cobimetinib intermissions and recurred while the molecule was resumed. Recurrence of cutaneous nodules was observed after initiation of trametinib combined with dabrafenib, and resolved once again with trametinib discontinuation. We believe that clinicians should be aware of this cutaneous adverse event in patients treated with combined therapy, which can lead to unfounded BRAF inhibitor treatment discontinuation and compromise the antitumor response. Our case suggests a class effect linked with the MEK inhibition pharmacodynamic activity. Finally, laboratory investigation and histopathological examination are mandatory to exclude other panniculitis etiologies and subcutaneous metastasis of melanoma.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Panniculitis Associated with MEK Inhibitor Therapy: An Uncommon Adverse Effect

Negulescu¹,

Deilhes²,

Sibaud³

et al. 2017

Case Rep Dermatol

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“…The usual cutaneous side effects consist of verrucous papillomas, present in about 80% of the patients, and hand-foot skin reaction, present in 60% of them. [9][10][11][12][13][14][15][16][17][18] Vemurafenib-induced neutrophilic panniculitis has been reported more commonly in women (9/10), and the mean age was 43.7 years, range 16-63 years. 1,3-FIGURE 1.…”

Section: Discussionmentioning

confidence: 99%

“…11,18 Confirmed cases have been described as lobular, septal, or mixed (both septal and lobular), and, although neutrophils usually predominate (9/17), instances with lymphocytes' predominance (5/17) or mixed cellularity (3/17) have also been published. Only 30 cases have been reported, 9-18 but 10 lack histopathological confirmation.…”

Section: Introductionmentioning

confidence: 99%

Vemurafenib-Induced Neutrophilic Panniculitis: A New Case and Review of the Literature

Vázquez‐Osorio¹,

Sánchez-Aguilar²,

García-Rodiño³

et al. 2016

The American Journal of Dermatopathology

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Vemurafenib has proved to be useful in the treatment of patients with unresectable or metastatic melanoma harboring the BRAF-V600E mutation, with better rates of overall and progression-free survival than previous treatments. Adverse cutaneous effects, such as alopecia, pruritus, photosensitivity reactions, verrucous keratosis, keratoacanthomas, or squamous cell carcinomas, have been described. Thirty cases of vemurafenib-associated panniculitis are available in the literature with variable clinical relevance. Only 9 of them exhibited definitive evidence of neutrophilic panniculitis. They all consist of multiple lesions, usually located in the lower limbs. Histopathologically, they have been described as predominantly neutrophilic, lymphocytic, or mixed, more commonly with lobular location. We report an additional case of neutrophilic panniculitis in a 45-year-old woman treated with vemurafenib for metastatic melanoma, presenting as a single lesion on his right leg. The lesion resolved spontaneously and did not need treatment reduction. The presentation of this condition with a single lesion is particularly challenging. Recognition of this association is important given the increasing use of vemurafenib and the potential implications of treatment withdrawal.

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“…[7] Very few cases of vemurafenib-associated vasculitis have been reported. [8–10] Vasculitis may be life-threatening depending on which organ is involved.…”

Section: Introductionmentioning

confidence: 99%

Systemic vasculitis associated with vemurafenib treatment

et al. 2016

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Rationale:Vemurafenib, an inhibitor of mutated B-rapidly accelerated fibrosarcoma, is frequently used in the treatment of melanoma and Erdheim–Chester disease (ECD) patients. Inflammatory adverse effects have been increasingly reported after vemurafenib treatment.Patient concerns and diagnose:We report 6 cases of vemurafenib-associated vasculitis, of whom a personal case of a 75-year-old man with history of ECD who developed purpura and rapidly progressive pauci-immune glomerulonephritis during treatment with vemurafenib.Intervention:In the 5 others cases from the literature, all patients presented skin vasculitis, and with joint involvement in 60% of them. Vemurafenib treatment was stopped (n = 3), continued at reduced doses (n = 1), or continued at the same dose (n = 2).Outcomes:Three patients (50%) received corticosteroids combined with cyclophosphamide (n = 1), and all achieved remission of vasculitis. One patient experienced vasculitis relapse after vemurafenib therapy was restarted.Lessons:Systemic vasculitis is a rare vemurafenib-associated adverse event that may be life-threatening.

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Vasculitis and panniculitis associated with vemurafenib

Cited by 22 publications

References 4 publications

Panniculitis Associated with MEK Inhibitor Therapy: An Uncommon Adverse Effect

Panniculitis Associated with MEK Inhibitor Therapy: An Uncommon Adverse Effect

Vemurafenib-Induced Neutrophilic Panniculitis: A New Case and Review of the Literature

Systemic vasculitis associated with vemurafenib treatment

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