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Dermatology Online Journal

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About

Dermatology Online Journal is an open-access, refereed publication intended to meet reference and education needs of the international dermatology community since 1995. Dermatology Online Journal is supported by the Department of Dermatology UC Davis, and by the Northern California Veterans Administration.

Volume 28, Issue 2, 2022

Review

Impact of an evolving regulatory landscape on skin cancer drug development in the U.S.

Background: There has been a rapid proliferation of FDA-approved medications with labeled indications for skin cancer over the last decade, with particular growth over the last 5 years. Objective: We aimed to evaluate the impact of an evolving U.S. regulatory framework on drug development programs to better understand current trends and regulatory considerations when adjudicating drug approvals for patients with skin cancer. Methods: We reviewed publicly-available regulatory documents of all systemic medications with a labeled indication for skin cancer. Results: We identified 130 FDA approvals that resulted in a unique indication, usage, formulation, or dosage change in skin cancer since 1949. Limitations: Publicly available data from the mid-to-late 20th century is limited. Conclusions: The therapeutic landscape in skin cancer has changed greatly since the first approval in 1949. In concert, regulatory medicine has also evolved over the last 70 years with the aim of ensuring safe and effective medicines for a diverse array of patients.

Original

Subscription-based and open access dermatology journals: the publication model dilemma

Medical journalism and the dissemination of peer-reviewed research serve to promote and protect the integrity of scholarship. We evaluated the publication models of dermatology journals to provide a snapshot of the current state of publishing. A total of 106 actively-publishing dermatology journals were identified using the SCImago Journal Rankings (SJR) citation database. Journals were classified by publication model (subscription-based and open-access), publishing company, publisher type (commercial, professional society, and university), MEDLINE-indexing status, and SJR indicator. Of these, 65 (61.32%) dermatology journals were subscription-based and 41 (38.68%) were open-access. In addition, 59 (55.66%) journals were indexed in MEDLINE and most were subscription-based (N=51) and published by commercial entities (N=54). MEDLINE-indexing status was significantly different across publisher types (P<0.001), access-types (P<0.001), and the top four publishers (P=0.016). Distribution of SJR indicator was significantly different across publisher types (P<0.001) and access-types (all journals, P=0.001; indexed journals only, P=0.046). More than 91% of MEDLINE-indexed titles were published by commercial entities, and among them, four companies controlled the vast majority. Discontinuation of access to any one of the top publishers in dermatology can significantly and disproportionately impact education and scholarship.

Commentary

Sexual orientation and gender identity (SOGI) data in dermatologic studies and opportunities for inclusion

Dermatologists serve a vast array of patients with unique backgrounds. The National Institutes of Health (NIH) designated members of sexual and gender minorities as underrepresented in scholarly literature. Our study examines the past 10 years of studies published in highly-cited dermatologic journals, surveying each study for common data collection of sexual orientation and gender identity (SOGI) in dermatological studies. We found representation of sexual and gender minorities to be increasing in dermatological studies but recommend that SOGI data be collected regularly just as any other common variable in dermatological patient studies.

Case Report

CD4/CD8 double-negative mycosis fungoides with large cell transformation and involvement of the lungs and leptomeninges

Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, classically has an indolent clinical course, with lesions slowly progressing from patch to plaque to tumor stage. In some cases, the late stages of disease involve extra-cutaneous dissemination to lymph nodes or viscera. Although this "Alibert-Bazin" type is the prototypic MF, there are several variants and subtypes of MF that may have different clinical implications for treatment and prognosis. We describe a woman whose disease course involved a variety of histopathologic and immunophenotypic variants including folliculotropic MF, granulomatous MF with loss of CD8, and then finally CD4/CD8 double-negative MF with large cell transformation and extra-cutaneous dissemination. Clinically her disease behaved as classic indolent stage IA MF for nearly two decades before transitioning to tumor stage and then, finally, involving the lungs and leptomeninges. It is important for physicians to be aware of the clinically relevant variants of MF as well as the possibility of transformation of previously stable disease both clinically and histopathologically.

Myopericytoma presenting as a painful dark subungual discoloration

Myopericytoma is an uncommon benign neoplasm that arises from the perivascular myoid cells. It typically presents as a painless well-circumscribed cutaneous or soft-tissue nodule, most commonly on the extremities of adults. Histologically, it is characterized by spindle-shaped myoid-appearing cells with a concentric arrangement in vessel walls, that are immunoreactive to alpha-smooth muscle actin and often for h-caldesmon, but negative for other smooth muscle markers. Herein, we present an unusual case of a painful subungual myopericytoma presenting as a dark subungual discoloration.

Case Presentation

A case of nivolumab-induced bullous pemphigoid successfully treated with dupilumab

A 76-year-old man came to our attention for the presence of itchy skin lesions localized on the trunk. The patient had a nodular melanoma removed two years earlier. Because of metastatic pulmonary melanoma, he underwent a lung lobectomy and began adjuvant therapy with nivolumab. After six months of treatment, the patient reported the appearance of itchy lesions on the trunk that were diagnosed as eczema and successfully treated with systemic corticosteroids. Upon corticosteroid discontinuation, the eruption relapsed presenting with erythematous macules, tense blisters, and erosions on the trunk and limbs. The presence of linear deposits of IgG and C3 at the dermo-epidermal junction and high serum levels of anti-BP180 antibodies confirmed the suspicion of nivolumab-induced bullous pemphigoid. Treatment with 0.6mg/kg methylprednisolone and 200mg/day doxycycline as well as nivolumab discontinuation induced temporary remission. After tapering methylprednisolone to 16mg/day, the patient developed new blisters. Therefore, dupilumab 300mg every other week was added with progressive improvement while methylprednisolone was tapered down and withdrawn after four months. After six months the patient was still in full clinical remission. Many cases of conventional bullous pemphigoid have been treated successfully with dupilumab, which can also be used safely in cancer patients without inducing overt immunosuppression.

A rare case of cutaneous metastasis of distal phalanx chondrosarcoma.

Chondrosarcoma is the second-most common primary malignant bone tumor but chondrosarcoma of small bones of the hand is extremely rare, representing less than 2% of all cases, with exceedingly rare skin metastases. Cutaneous metastases of chondrosarcoma represent less than 3% of all cutaneous metastases. According to PubMed, there are only four previous case reports of cutaneous metastases originating from chondrosarcoma of small bones of the hand. We present an additional case of cutaneous metastases of phalangeal chondrosarcoma with a unique immunophenotype.

Cutaneous hydrophilic polymer emboli following endovascular repair of an abdominal aortic aneurysm: a case and review of literature

Hydrophilic polymer embolism (HPE) is a rare iatrogenic complication of the use of polymer-coated intravascular devices, which may affect several organ systems including the skin. Herein, we present a patient who developed a cutaneous eruption with associated neurologic manifestations secondary to localized HPE. This is a potentially underdiagnosed, life-threatening complication and physicians should consider HPE when evaluating skin eruptions in patients who have undergone endovascular procedures.

Interstitial granulomatous dermatitis and concurrent immunotherapy associated encephalitis with nivolumab and ipilimumab

Immune-related adverse events (irAEs) are common in patients receiving immune checkpoint inhibitors for metastatic melanoma and other advanced malignancies. Cutaneous, gastrointestinal, and endocrine (thyroid) irAEs are most prevalent, whereas neurologic irAEs are rare. We present a 73-year-old man with dementia and metastatic melanoma who developed immunotherapy-associated encephalitis and subsequently, interstitial granulomatous dermatitis with nivolumab/ipilimumab. High-dose corticosteroids successfully treated both conditions, though he never regained his baseline mental status. We review the literature on interstitial granulomatous dermatitis and encephalitis with immunotherapy.

Acroangiodermatitis presenting as unilateral hypertrophic verrucous plaques

Acroangiodermatitis (AAD)[KL1] is a rare vasoproliferative disorder often involving the extremities that has been classified into two variants. Mali-type AAD is more common and associated with chronic venous stasis. Stewart-Bluefarb syndrome[KL2], the other variant, is associated with underlying arteriovenous abnormalities. Mali-type AAD is a relatively benign diagnosis but it may mimic more harmful etiologies such as Kaposi sarcoma both clinically and histologically. A 67-year-old woman with a history of varicose veins, deep vein thrombosis, stroke, and obesity presented to our outpatient clinic with verrucous red-brown papules and plaques on her right lower extremity worsening for three years. Biopsy was consistent with a diagnosis of Mali-type AAD. Providers should be aware of AAD and its variants to accurately differentiate it from more harmful entities.

Photo Vignette

Degenerative collagenous plaques of the hands in an elderly woman

Degenerative collagenous plaques of the hands is an underrecognized acquired dermatosis characterized by slowly progressive linear depressed bands appearing symmetrically at the margins of palmar and dorsal skin of the hands. It is more common in the elderly and is believed to result from chronic pressure and ultraviolet radiation. We present an elderly woman with degenerative collagenous plaques of the hands to highlight an underrecognized rare dermatosis.

Advanced squamous cell carcinoma with massive cranial invasion: walking around without a forehead

Squamous cell carcinomas with widespread invasion of the skull, meninges and brain parenchyma are extremely rare. Herein, we present an 86-year-old man with an 18-year history of sunburn who developed a large osteodestructive SCC that invaded through the frontal bone, frontal sinuses, and the dura mater. No neurological signs or symptoms or distant metastasis were noted. Such cases arise through patient neglect or lack of access to care and pose many challenges as lack of symptoms tend to deceive patients from seeking medical advice. Urgent aggressive treatment by a multidisciplinary team is paramount to achieving a successful outcome.

Letter

Recruitment Advertisement

Position Title: Basic Scientist

The University of California, Davis, School of Medicine, the Department of Dermatology is currently recruiting for a full-time basic research position in the series of Ladder rank or In-Residence at the Associate or Full Professor rank. Appointees to this position will be predominantly engaged in research, but also participate in teaching and engage in University and public service. This position may be 100% or 50/50 appointment. Professor In-Residence titles are intended to be used for individuals supported by non-State funds.