A case of radiation-induced bullous morphea/lichen sclerosus overlap in a breast cancer patient.

Radiation induced morphea (RIM) is an increasingly common complication of radiation treatment for malignancy as early detection has made more patients eligible for non-surgical treatment options. In many cases, the radiation oncologist is the first person to learn of the initial skin changes, often months before a dermatologist sees them. In this paper we present a breast cancer patient who developed a rare bullous variant of RIM, which delayed her diagnosis and subsequent treatment. It is imperative to diagnose RIM early as it carries significant morbidity and permanent deformity if left untreated. The lesions typically present within 1 year of radiation therapy and extend beyond the radiated field. RIM is often mistaken for radiation dermatitis or cellulitis. Bullae, when present, are often hemorrhagic in appearance, which can serve as another clinical clue. It is important to refer these patients for a full gynecologic exam as there can be concurrent anogenital lichen sclerosus et atrophicus which is both debilitating and carries a long term risk for squamous cell carcinoma. Treatment with systemic agents is often necessary, and can be managed by a dermatologist. The most proven regimen in the literature appears to be methotrexate, with our without concurrent narrow band UVB phototherapy.

Lichenoid Dermatitis From Interferon alpha-2a in a Patient With Metastatic Renal Cell Carcinoma and Seronegative HCV.

Cutaneous reactions to interferon, including a lichenoid drug reaction, are most commonly reported in patients undergoing treatment for hepatitis C virus (HCV) infection. There have been case reports of interferon-induced lichen planus in seronegative HCV patients with lymphoproliferative disorders and melanoma. We report the case of a 71-year-old man undergoing treatment with interferon for metastatic renal cell carcinoma (RCC) who developed an eruption 2 months after starting interferon. Clinical and histological findings from biopsies supported a diagnosis of interferon-induced lichen planus. To our knowledge, this is the first known case of a lichenoid drug eruption from interferon in a seronegative HCV patient with metastatic RCC.

J Drugs Dermatol. 2017;16(7):714-716.

Diverse types of dermatologic toxicities from immune checkpoint blockade therapy.

Immunomodulatory drugs that leverages host immune mechanisms to destroy tumor cells have been met with great promise in the treatment of cancer. Immunotherapy, targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have shown tremendous improvements in the survival of patients with advanced solid tumors. However, the development of dermatologic toxicity (DT) is a consequence to immunotherapy. Review of published reports of the DT to immunotherapy revealed patients receiving anti-CTCLA-4 antibody or anti-PD-1/PD-L1 antibody often develop a DT of any type and grade. In this article, of the 3825 patients who were treated with anti-PD-1 and of 556 patients receiving anti-PD-L1, DT of any type and grade were reported in 1474 (∼39%) and 95 (∼17%) of patients, respectively. The emergence of specific types of DT to immunotherapy is beginning to be recognized can be categorized into four groups: (a) inflammatory, (b) immunobullous, (c) alteration of keratinocytes and (d) alteration of melanocytes. Lichenoid dermatitis and bullous pemphigoid appear to be DT more associated with anti-PD-1/PD-L1 antibody. The DT profile in patients receiving immunotherapy is diverse, and early recognition of specific types of DT that clinicians may encounter is critical for optimal patient care.

Graft-versus-host disease-associated angiomatosis: a clinicopathologically distinct entity.

BACKGROUND: Chronic graft-versus-host disease (GVHD) may present with various cutaneous manifestations. Isolated case reports describe eruptive angiomas in this setting. OBJECTIVE: We sought to provide a clinical and pathologic description of vascular proliferations in patients with GVHD. METHODS: Cases of documented GVHD associated with vascular proliferations were collected from the National Institutes of Health, Ohio State University, and MD Anderson Cancer Center. RESULTS: Eleven patients with a diagnosis of GVHD who developed vascular proliferations were identified. All patients manifested sclerotic type chronic GVHD of the skin. Vascular lesions were first documented a median of 44 months after transplantation and occurred primarily on the lower extremities or trunk. Histopathology revealed anastomosing networks of thin-walled vascular proliferations in a vague lobular growth pattern, with overlying epidermal acanthosis, peripheral collarette, ulceration, and disorganized fibroblast-rich and fibrotic stroma. Improvement was noted in 1 patient treated with propranolol and sirolimus and 1 patient with electrocautery. LIMITATIONS: Given the retrospective nature of the study, the overall incidence of vascular lesions in patients with GVHD is unknown. Histopathology was present for review on only 3 of 11 patients. CONCLUSION: The phenomenon of vascular lesions appears to be relatively specific for sclerotic type chronic GVHD when compared with other fibrosing diseases. We propose the term "graft-versus-host disease-associated angiomatosis" to describe this entity.

Post-varicella-zoster virus granulomatous dermatitis: a report of 2 cases.

Granulomatous dermatitis (GD) is known to occur following varicella-zoster virus (VZV) infection. Lesions may appear at varying times after the acute eruption in both immunosuppressed and immunocompetent hosts. The etiology of GD is unclear, and findings of VZV in the lesions often are inconsistent. We describe 2 immunocompromised patients who presented with GD following VZV infection; their lesions were examined for the presence of VZV. We also review the literature on postzoster GD.

Annular plaques: An unusual manifestation of graft-versus-host disease.

Chronic cutaneous graft-versus-host disease (GVHD) classically presents with lichenoid papules or sclerotic plaques. This case highlights an unusual clinical manifestation of chronic GVHD and demonstrates that the skin morphology of chronic GVHD and cutaneous lymphoma may be similar. We report for the first time a case of annular scleroderma-like graft-versus-host disease in a patient following allogeneic stem cell transplant for CD30+ anaplastic large cell lymphoma. Treatment of these skin lesions with ultraviolet A1 (UVA1) phototherapy resulted in significant improvement.

Graft-versus-host disease: part I. Pathogenesis and clinical manifestations of graft-versus-host disease.

Approximately 25,000 allogeneic hematopoietic cell transplants are performed worldwide each year for a variety of malignant and non-malignant conditions. Graft-versus-host disease represents one of the most frequent complications and is a major source of long-term morbidity and mortality. Whereas acute graft-versus-host disease is induced by recognition of host tissues as foreign by immunocompetent donor cells, the pathogenesis of chronic graft-versus-host disease is not as well understood, and continues to be a major treatment challenge. Part I of this two-part series reviews the epidemiologic factors, classification, pathogenesis, and clinical manifestations of acute and chronic graft-versus-host disease. Part II discusses the topical, physical, and systemic treatment options available to patients with graft-versus-host disease.

Graft-versus-host disease: part II. Management of cutaneous graft-versus-host disease.

Dermatologists are ideally suited to manage the various cutaneous sequelae of graft-versus-host disease (GVHD) outlined in part I of this review. However, the complexity of the patient with GVHD, including comorbidities, potential drug interactions related to polypharmacy, and the lack of evidence-based treatment guidelines, are significant challenges to optimizing patient care. In this section, we will provide an outline for the role of the dermatologist in a multispecialty approach to caring for patients with GVHD.

Actinic granuloma occurring in an unusual association with cutaneous B-cell chronic lymphocytic leukemia.

Granulomatous cutaneous reactions are well described in association with T-cell non-Hodgkin lymphoma and Hodgkin lymphoma, but are rarely seen in association with B-cell non-Hodgkin lymphoma or leukemia. We report a case of a 65-year-old woman with B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who presented with multiple, tender, firm pink papules on the face, upper trunk and upper extremities 6 years after diagnosis of CLL. Biopsy revealed both palisading granulomatous dermatitis consistent with actinic granuloma and a dense perivascular lymphocytic infiltrate consistent with the patient's known history of leukemia. This is an unusual manifestation of cutaneous B-cell CLL that is rarely seen.

Extended-field irradiation and intracavitary brachytherapy combined with cisplatin and amifostine for cervical cancer with positive para-aortic or high common iliac lymph nodes: results of arm II of Radiation Therapy Oncology Group (RTOG) 0116.

OBJECTIVES: Radiation Therapy Oncology Group (RTOG) 0116 was designed to test the ability of amifostine (Ethyol; MedImmune LLC, Gaithersburg, MD), a cytoprotective agent, to reduce the acute toxicity of combined therapy with extended-field irradiation, brachytherapy, and cisplatin chemotherapy in patients with cervical cancer with para-aortic or high common iliac disease. This report presents the results of part 2. MATERIALS AND METHODS: Radiation Therapy Oncology Group 0116 was a 2-part trial. Part 1 delivered extended-field irradiation, brachytherapy, and cisplatin; part 2 added amifostine and required 16 evaluable patients to assess an improved toxicity profile. Eligibility included evidence for high common iliac or para-aortic metastasis. Patients were treated for a total dose of 45 Gy in 25 fractions with intracavitary irradiation. Intensity-modulated radiation therapy was not allowed. The final point A dose was 85 Gy low-dose rate equivalent. High-dose rate techniques were allowed. The positive para-aortic and iliac nodes were to be boosted to 54 to 59.4 Gy. Amifostine at 500 mg was to be delivered with every fraction of radiotherapy. RESULTS: The study opened on August 1, 2001, and closed March 3, 2007, after accruing 45 patients, 18 for the second part with amifostine. This analysis reports the primary end point for the patients entered on part 2 of the study. Three patients were excluded, one was ineligible, and 2 withdrew. The median follow-up was 22.9 months (range, 6.5-45.4 months). The median dose of amifostine delivered was 5000 mg (range, 500-13,500 mg). Thirteen patients (87%) experienced an acute grade 3/4 toxicity (excluding grade 3 leukopenia). This compared to an 81% rate in part 1 of the trial. The estimated median survival was 34.8 months with a 20% late grade 3/4 toxicity rate. CONCLUSIONS: Amifostine, as delivered in this study, did not reduce acute toxicity in this patient population.

Ulcerated plaque under a ruby ring in an immunosuppressed patient.

We report a primary inoculation fungal infection in a 76-year-old man with acute myeloid leukemia. The patient presented with a painful red plaque located where he routinely wore a ruby ring. Histopathology revealed multiple branching septate hyphae. Cultures confirmed Fusarium and Candida parapsilosis infection. A short discussion of these organisms follows.

Longitudinal melanonychia induced by capecitabine.

Capecitabine is an oral prodrug of 5-fluorouracil (5-FU), used in the treatment of metastatic colon and breast cancers; it is also under investigation for use in gastric cancers. Multiple cutaneous adverse effects have been reported with the use of capecitabine including acral erythema, pyogenic granulomas, inflammation of actinic keratoses, cutaneous and mucosal hyperpigmentation, leopardlike vitiligo, radiation recall, onycholysis, onychomadesis, and subacute cutaneous lupus. To our knowledge, no cases of capecitabine-induced linear melanonychia have been reported to date in the literature.

Four patients with cutaneous metastases from medullary thyroid cancer.

Cutaneous metastasis from thyroid cancer, especially medullary thyroid cancer (MTC) is rare. We report four patients with cutaneous metastases from sporadic MTC, three women and one man, aged 50 to 69 years. They presented different cutaneous lesions phenotypes. The first patient had a remote history of MTC and initial presentation of the recurrence was a rapidly progressing cutaneous lesion; on subsequent disease staging, widely metastatic disease was discovered. The other three patients developed cutaneous metastases in the presence of known distant metastases, indicating systemic spread of thyroid cancer. Definitive diagnosis of cutaneous metastases of MTC was made on biopsy of the lesions with cells that stained positive for neuroendocrine markers. Accurate diagnosis of cutaneous metastasis from MTC is important because it is a negative prognostic factor indicative of multisystemic disease. Thus, MTC metastases should be included in the differential diagnosis of erythematous maculopapular eruptions and nodular lesions of the skin, especially when these metastases occur in the upper part of the body and if the patient has a history of MTC. The appearing of cutaneous metastasis is a negative prognostic factor since all the patients here described died within one year from the diagnosis of cutaneous metastases.

Adult Henoch-schönlein purpura in a patient with myelodysplastic syndrome and a history of follicular lymphoma.

GOAL: To understand Henoch-Schönlein purpura (HSP) to better manage patients with the condition. OBJECTIVES: Upon completion of this activity, dermatologists and general practitioners should be able to: 1. Describe the criteria for diagnosing HSP. 2. Explain the association of malignancy and HSP. 3. Discuss the prevalence of HSP in adults. Henoch-Schönlein purpura (HSP) is a systemic leukocytoclastic vasculitis involving arterioles and venules most commonly in the skin, glomeruli, and gastrointestinal tract. In skin, it is associated with IgA deposition around dermal blood vessels. While an exact cause of HSP has not been elucidated, several processes have been implicated in its development, including infections; drugs; and allergic, rheumatologic, and neoplastic diseases. We present a 57-year-old woman with a history of follicular lymphoma who developed HSP likely associated with myelodysplastic syndrome. This case is clinically significant because the patient was thought to be in remission of her hematologic disease until her skin findings prompted further evaluation. Her diagnosis of HSP was based on clinical presentation with palpable purpura and abdominal pain, and was confirmed with biopsy and immunohistochemical analyses of purpuric papules demonstrating leukocytoclastic vasculitis and strong anti-IgA labeling in the dermal endothelial cells consistent with immunocomplex deposition. The occurrence of vasculitis and malignant disease in the same patient often is difficult to interpret, as some patients may exhibit both diseases independently and by chance, while others may have vasculitis as a paraneoplastic syndrome. We review cases of adult HSP associated with malignancy in the literature.

Approach to the morbilliform eruption in the hematopoietic transplant patient.

Morbilliform eruptions occur frequently in the hematopoietic transplant population. The differential diagnosis includes drug reaction, viral exanthem, and cutaneous graft versus host disease. Using a typical patient case, we discuss the diagnostic approach to this clinical problem.