Catherine G. Chung

Characteristic purpura of the ears, vasculitis, and neutropenia–a potential public health epidemic associated with levamisole-adulterated cocaine

BACKGROUND Dermatologists at the University of California, San Francisco recently reported two patients in the online Journal of the American Academy of Dermatology with purpura presumably induced by levamisole in contaminated cocaine. Levamisole-induced vasculitis and neutropenia has been reported elsewhere in the United States and Canada. Up to 70% of cocaine in the United States could be contaminated. OBJECTIVE We sought to describe similar cases of vasculitis associated with cocaine use. METHODS This is a retrospective case series. RESULTS We report 6 remarkably similar patients seen over just the past few months with retiform purpura on the body and tender purpuric eruptions, necrosis, and eschars of the ears after cocaine use in New York and California. All of these patients had positive perinuclear antineutrophil cytoplasmic antibody values and 3 of the 6 also had an associated neutropenia. Direct immunofluorescence studies suggested an immune complex-mediated vasculitis. LIMITATIONS This case series is descriptive in nature and, because testing is not easily performed, we did not test for levamisole in the serum or blood to prove this is the causative agent. CONCLUSION It appears the use of cocaine is associated with the peculiar clinical findings of ear purpura, retiform purpura of the trunk, and neutropenia. We believe this case series may represent the tip of the iceberg as a looming public health problem caused by levamisole. Although the direct causal relationship may be difficult to establish, the astute dermatologist or primary care physician should be able to recognize the characteristic skin lesions and should be wary of the potential development of agranulocytosis.

Cutaneous T cell Lymphoma: an Update on Pathogenesis and Systemic Therapy

Mycosis fungoides (MF) and its leukemic variant, Sézary syndrome (SS), are malignancies of skin-homing T cells that comprise the majority of cutaneous T cell lymphomas (CTCL). Treatment of CTCL is limited and can be approached by skin-directed therapy or systemic therapy. Recent investigations into the pathogenesis of MF and SS have broadened the therapeutic targets; here, we review emerging concepts in the pathogenesis of MF and SS as well as novel and traditional systemic therapies for MF and SS. These include histone deacetylase inhibitors (vorinostat, romidepsin, panobinostat, and belinostat), monoclonal antibodies (alemtuzumab, brentuximab vedotin, and mogamulizumab) and single-agent cytotoxic chemotherapeutic agents (e.g., pralatrexate, doxorubicin, bendamustine, and forodesine), as well as multi-agent chemotherapy regimens.

Romidepsin: evidence for its potential use to manage previously treated cutaneous T cell lymphoma

Introduction: Cutaneous T cell lymphoma (CTCL) encompasses a heterogeneous group of neoplasms of skin-homing T cells, which includes mycosis fungoides, the most common form, and Sézary syndrome, the leukemia equivalent of mycosis fungoides. Histone deacetylase inhibitors are currently under investigation for their therapeutic value in a variety of conditions. Through multiple mechanisms, they induce apoptosis or inhibition of tumor cell growth. Some studies have also shown histone deacetylase inhibitors to have synergistic activity with existing therapeutic agents in selected conditions. Romidepsin is a histone deacetylase inhibitor with a promising efficacy and safety profile that may represent a valuable treatment alternative for patients with treatment-resistant mycosis fungoides and Sézary syndrome. Aims: To review emerging evidence regarding the use of romidepsin in the management of treatment-resistant CTCL. Evidence review: There is evidence that romidepsin can induce significant and durable responses in patients with refractory CTCL. In two independent Phase II trials including a total of 167 patients with CTCL, there was an overall response rate of 34% with a partial response of 28% and complete response rate of 6%. The most frequent toxicities reported from the Phase II trials were nausea, vomiting, fatigue, anorexia, and dysgeusia. Clinical potential: Romidepsin may be an effective therapeutic option for patients with CTCL who have had treatment failure with multiple standard treatment modalities.

Cutaneous involvement in multiple myeloma (MM): A case series with clinicopathologic correlation

BACKGROUND Disease-specific skin lesions are rare in patients with multiple myeloma (MM). OBJECTIVE We sought to further characterize the clinical and pathologic features of patients with cutaneous involvement with MM. METHODS We identified 13 patients with cutaneous lesions of MM. RESULTS Cutaneous lesions consisted of pink, red, and violaceous papules, nodules, and/or plaques that varied in size. Histopathology revealed atypical plasma cells with occasional plasmablastic features. MM had aggressive biologic features and was at an advanced stage in the majority of patients. Despite aggressive management, including chemotherapy and stem-cell transplantation, most patients died of progressive disease within a few months after the development of cutaneous lesions. LIMITATIONS The study group was relatively small. CONCLUSIONS Cutaneous involvement with MM is associated with aggressive biologic behavior and short survival.

Halo nevus: review of the literature and clinicopathologic findings

and BCC. Expression of bKlotho is reduced in secondary tumors of NS. As post-zygotic HRAS or KRAS mutations and the constitutive activation of Ras–Raf–MAPK and PI3K–Akt signaling pathways are observed in NS, the reduction of bKlotho expression may enhance Akt signaling in secondary tumors in the epidermis in NS. Similarly, it is possible that the reduction of bKlotho expression enhances Akt signaling in the epidermis during the development of non-melanoma skin cancers. In summary, this is the first study to demonstrate the expression of bKlotho to be reduced in SCC and BCC.

Erythema Ab Igne due to Heating Pad Use: A Case Report and Review of Clinical Presentation, Prevention, and Complications.

Erythema ab igne is an asymptomatic cutaneous condition caused by exposure to heat. Cases of erythema ab igne may prove to be diagnostically challenging due to lack of familiarity with the condition. While this dermatosis carries a favorable prognosis, nonmelanoma skin cancers have been reported to arise within lesions of erythema ab igne. Erythema ab igne is preventable, and, thus, clinicians should provide education regarding safe use of heating devices to patients using these products in both outpatient and inpatient settings.

Recommendations for Solid Organ Transplantation for Transplant Candidates with a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma

Advancements in solid organ transplantation successfully extend the lives of thousands of patients annually. The tenet of organ stewardship aims to prevent the futile expenditure of scarce donor organs in patient populations with high mortality risk, to the detriment of potential recipients with greater predicted life expectancy. The development of skin cancer posttransplantation portends tremendous morbidity, adversely affecting quality of life for many transplant recipients. This special article, provided by of members of the International Transplant Skin Cancer Collaborative (ITSCC), will provide the transplant professional with a consensus opinion and recommendations as to an appropriate wait period pretransplantation for transplant candidates with a history of either cutaneous squamous cell carcinoma, malignant melanoma, or Merkel cell carcinoma.

Necrobiosis lipoidica occurring in a patient with rheumatoid arthritis on concurrent tumor necrosis factor-α inhibitor therapy

Necrobiosis lipoidica (NL) is a chronic granulomatous skin disorder with unclear pathogenesis. Classic, welldeveloped lesions of NL feature patches or plaques with an atrophic, slightly depressed, often shiny yellow–brown center. The border of these lesions frequently demonstrates a well-defined inflammatory edge that may be raised and red to purple in color. The pretibial areas are the most commonly affected location, and less frequently lesions may be seen on the upper extremities, face, and scalp. Up to 35% of cases demonstrate ulceration, frequently following minor trauma. The average age of onset is in the fourth decade, but cases occurring in children and the elderly have also been reported. While the majority of cases are idiopathic, NL has been associated with various systemic and chronic diseases, including diabetes mellitus, sarcoidosis, rheumatoid arthritis (RA), autoimmune thyroid disease, and inflammatory bowel disease. The main histopathologic features of an established lesion of NL are those of horizontally oriented palisading granulomas composed of histiocytes, lymphocytes, and, to a lesser extent, plasma cells that involve the full thickness of the dermis. The process may extend into the subcutaneous adipose tissue as well, lending a clinical and histopathologic picture of panniculitis.

Lentigo Maligna Melanoma With Local and Distant Blue Nevus-like Metastases.

Melanoma or melanoma metastases can rarely mimic blue nevi clinically and/or histologically, presenting a diagnostic pitfall for both the clinician and the dermatopathologist. We report a case of an invasive lentigo maligna melanoma with subsequent development of multiple, cutaneous blue nevus-like localized metastases followed by a distant metastasis, heralding widespread systemic metastases.

Other Chemotherapeutic Agents in Cutaneous T-Cell Lymphoma

Traditional chemotherapies, interleukins, phosphorylase inhibitors, and proteasome inhibitors are important therapies available to patients with cutaneous T-cell lymphoma (CTCL). Traditional chemotherapies, both in combination and as single agents, are commonly used in relapsed, refractory CTCLs that behave in an aggressive manner. Interleukins, phosphorylase inhibitors, and proteasome inhibitors are less commonly used but data support a role in patients with more refractory disease.