Mark A. Bechtel

The role of Malassezia in atopic dermatitis affecting the head and neck of adults

Atopic dermatitis is a common chronic skin condition. A subset of patients with head and neck dermatitis may have a reaction to Malassezia flora fueling their disease. Although there are no documented differences in Malassezia species colonization, patients with head and neck atopic dermatitis are more likely to have positive skin prick test results and Malassezia-specific IgE compared with healthy control subjects and patients with atopy without head and neck dermatitis. There is no clear relationship with atopy patch testing. The reaction to Malassezia is likely related to both humoral- and cell-mediated immunity. Clinically, Malassezia allergy may be suspected in patients with atopic dermatitis and: (1) head and neck lesions; (2) exacerbations during adolescence or young adulthood; (3) severe lesions recalcitrant to conventional therapy; and (4) other atopic diseases. There is literature to suggest that these patients will benefit from a 1- to 2-month course of daily itraconazole or ketoconazole followed by long-term weekly treatment.

Basal cell carcinoma: Stressful life events and the tumor environment

CONTEXT Child emotional maltreatment can result in lasting immune dysregulation that may be heightened in the context of more recent life stress. Basal cell carcinoma (BCC) is the most common skin cancer, and the immune system plays a prominent role in tumor appearance and progression. OBJECTIVE To address associations among recent severe life events, childhood parental emotional maltreatment, depression, and messenger RNA (mRNA) coding for immune markers associated with BCC tumor progression and regression. DESIGN We collected information about early parent-child experiences, severe life events in the past year as assessed by the Life Events and Difficulties Schedule, depression, and mRNA for immune markers associated with BCC tumor progression and regression from patients with BCC tumors. SETTING University medical center. PARTICIPANTS Ninety-one patients with BCC (ages, 23-92 years) who had a previous BCC tumor. MAIN OUTCOME MEASURES The expression of 4 BCC tumor mRNA markers (CD25, CD3ε, intercellular adhesion molecule 1, and CD68) that have been linked to BCC tumor progression and regression were assessed in BCC tumor biopsy specimens. RESULTS Both maternal and paternal emotional maltreatment interacted with the occurrence of severe life events to predict the local immune response to the tumor (adjusted P = .009 and P = .03, respectively). Among BCC patients who had experienced a severe life event within the past year, those who were emotionally maltreated by their mothers (P = .007) or fathers (P = .02) as children had a poorer immune response to the BCC tumor. Emotional maltreatment was unrelated to BCC immune responses among those who did not experience a severe life event. Depressive symptoms were not associated with the local tumor immune response. CONCLUSIONS Troubled early parent-child relationships, in combination with a severe life event in the past year, predicted immune responses to a BCC tumor. The immunoreactivity observed in BCCs and the surrounding stroma reflects an anti-tumor-specific immune response that can be altered by stress.

Treatment of Recalcitrant Generalized Morphea With Infliximab

A 66-year-old white woman with a history of hypertension and degenerative arthritis was seen in July 2003 by her primary care physician (PCP) for erythematous and sclerotic patches on her trunk. A skin biopsy specimen taken by the PCP at that time was interpreted (by an outside pathology laboratory) to indicate granuloma annulare. The patient began treatment with systemic corticosteroids and ceased taking her antihypertensive medication. However, her cutaneous symptoms continued to progress, and she was referred to our clinic in January 2004. At that time, the patient denied any illnesses prior to her skin eruption and noted that the only change in her medications was from lisinopril to valsartan. A review of systems found no shortness of breath, dysphagia, worsening of chronic joint symptoms, or Raynaud phenomenon. The patient was noted to have extensive white sclerotic patches and a few eczematous inflammatory patches on the upper chest, breasts (excluding the areola), upper abdomen, flanks, and proximal extremities (Figure 1). Her skin was firm and sclerotic on palpation. No sclerodactyly was present. A skin biopsy specimen was obtained. Light microscopic examination revealed a striking pandermal sclerosing reaction. The collagen bundles were of wider caliber and oriented parallel to the long axis of the epidermis. In addition, the overlying epidermis was attenuated with prominent hyperkeratosis. The subjacent papillary dermis had a hyalinized appearance with vascular dropout. The findings were compatible with an overlap between morphea and lichen sclerosus et atrophicus (LS&A). In situ hybridization studies demonstrated focal staining of the endothelium for cytomegalovirus (CMV) and tumor necrosis factor (TNF) RNA transcript expression. Direct immunofluorescence showed deposits of C5b-9 within the microvasculature most compatible with a humorally mediated microangiopathy syndrome (Figure 2). Serologic studies revealed positive anti-CMV IgM and IgG. However, the findings of antinuclear antibody assays, extractable nuclear protein antibody tests, an interstitial lung battery, complete blood cell count, and comprehensive chemical analysis were all within normal limits, as was the erythrocyte sedimentation rate. The patient was also found to be very hypertensive and resumed taking antihypertensive medications along with class 1 topical corticosteroids. Figure 1. Eczematous inflammatory patches.

Tinea capitis among children in the Columbus area, Ohio, USA

Tinea capitis is a fungal infection of the hair follicles of the scalp. In the US, the most common organisms have traditionally been Trichophyton tonsurans, and occasionally Microsporum canis. This study was designed to examine patterns of organisms causing tinea capitis and determine factors associated with infection. A retrospective database analysis was conducted to locate records of patients with tinea capitis from May 2001 to May 2006 at Nationwide Children’s Hospital in Columbus, OH. Descriptive statistics, frequency analysis, chi‐squared test, and Student’s t‐test were performed to evaluate types of causative organisms and associated patient characteristics. One hundred and eighty‐nine charts of patients with a positive scalp culture for tinea capitis were located. Trichophyton tonsurans (88.9%) was the foremost causative agent followed by Trichophyton violaceum (4.2%). Tinea capitis was more prevalent among African Americans and was more common in urban areas (P < 0.05). Children of African descent inhabiting urban settings were most vulnerable to tinea capitis. The most common organism isolated in this retrospective study was T. tonsurans. Trichophyton violaceum and Trichophyton soudanense were also isolated, which are not commonly reported causes of tinea capitis in the US.

Metastatic basal cell carcinoma presenting with unilateral upper extremity edema and lymphatic spread

Basal cell carcinoma (BCC), the most common human malignancy, metastasizes in 0.0028% to 0.5% of cases, usually to the lymph nodes, lungs, bones, and skin. After metastatic spread of BCC, survival averages 1 to 2 years. Chemotherapy, radiotherapy, and surgery are treatment options. We describe metastatic basal cell carcinoma to the skin presenting with unilateral upper extremity edema.

Gender specific association of child abuse and adult cardiovascular disease in a sample of patients with Basal Cell Carcinoma

OBJECTIVE The aim of this study is to examine whether child abuse or neglect is more strongly associated with adult cardiovascular disease, and whether these associations differ by gender. METHODS A total of 116 participants (mean age 57.75 years) reported their experience of childhood maltreatment using the well-validated Childhood Experience of Care and Abuse Questionnaire. Cardiovascular disease was assessed using the Older Adults Resources Survey Multidimensional Functional Assessment Questionnaire. RESULTS Child abuse but not neglect was significantly associated with adult cardiovascular disease. The significant relationship between child abuse and cardiovascular disease was specific to women. CONCLUSION The results of this study indicate that being abused as a child is significantly associated with cardiovascular disease in adulthood, particularly among women.

Treatment of refractory pemphigus erythematosus with rituximab

XXX Correspondence Treatment of refractory pemphigus erythematosus with rituximab Pemphigus erythematosus is an autoimmune disease with combined features of pemphigus foliaceus and lupus erythematosus. The disease manifests itself on sun-exposed skin as small, flaccid bullae with scaling and crusting. Generally the scalp, face, upper chest, and back are involved, with lesions of the face presenting in the typical butterfly distribution seen in systemic lupus erythematosus (SLE). An 18-year-old female presented in November 2004 for evaluation of keratotic hyperpigmented papules and plaques on the face, upper trunk, and proximal extremities (Fig. 1). Biopsy of the lesions revealed acantholysis within the granular cell layer with concomitant interface dermatitis. DIF showed intercellular deposits of IgG and C3 along with an interrupted band of +1/3 granular deposition of IgM along the dermal epidermal junction. The findings were consistent with the diagnosis of pemphigus erythematosus. Our patient showed no response to several months of dapsone plus topical corticosteroids (at escalating doses). She responded to high dose prednisone (60 mg/d), but flared upon tapering to 20 mg/d. She also had failed mycophenolate mofetil (Cellcept) and cyclosporine as steroid sparing agents. In February 2006 she was started on 40 mg of prednisone plus weekly infusions of 375 mg/m rituximab, and showed significant reduction in her symptoms by June 2006. On exam she showed regression of the majority of her skin lesions, leaving post-inflammatory hyperpigmentation (Fig. 2). The patient’s desmoglein 1 antibody level had decreased from 336.9 prior to treatment to 147 by the end of her 12-week course. According to a search of English literature, our case represents the first case of pemphigus erythematosus treated successfully with rituximab. Pemphigus erythematosus is an antibody-mediated autoimmune disease directed at desmoglein 1, a desmosomal protein important in keratinocyte adhesion, resulting in intraepidermal bullae. Treatment for pemphigus erythematosus has relied heavily on the use of systemic steroids, with some reports of use of dapsone, azathioprine, and cytotoxic agents such as cyclophosphamide and methotrexate. Rituximab is indicated for the treatment of patients with relapsed or refractory, low-grade or follicular, CD20positive, B cell non-Hodgkin lymphoma. It is a promising agent for the treatment of diseases mediated by B cells, and has been reported to be effective in pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, as well as refractory pediatric SLE. Rituximab is a chimeric murine/human monoclonal antibody. This IgG1 targets the CD20 antigen expressed by pre-B, immature and mature B cells and regulates early steps in the activation and differentiation of these cells. The binding of rituximab to CD20 results in cell lysis via complementand antibody-dependent cytotoxicity. CD20 is not expressed on stem cells or plasma cells and hence depletion of the B cell subpopulation is transient and does not affect immunoglobulin production. We believe that rituximab with its anti-B cell activities, namely activation and proliferation, has led to suppression of antidesmoglein antibody production leading to remission in our patient. The side-effects of rituximab are frequent but usually not serious. These include night sweats, hypersensitivity reactions, pruritus, urticaria, bacterial infections, and shivering during infusion. Uncommon cutaneous side-effects include Stevens–Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, toxic epidermal necrolysis, serum sickness, vasculitis, and severe mucocutaneous reactions, some with fatal outcome. Non-cutaneous side-effects include fatal infusion reactions, hepatitis B reactivation with related fulminant hepatitis and serious or life threatening cardiac arrhythmias. In conclusion, Rituximab is a novel alternative treatment for pemphigus erythematosus, especially recalcitrant cases or Figure 1 Pre-treatment lesions Figure 2 Post-treatment chest lesions

Magnetic resonance elastography and transient elastography as non‐invasive analyses for liver fibrosis: can they obviate the need for liver biopsy in psoriasis patients treated with methotrexate?

The liver biopsy has been regarded as the reference standard method of monitoring hepatic fibrosis in psoriasis patients treated with methotrexate. It has also been subject to concerns over sampling error, internal and external variability, and potential for morbidity and mortality. During the past two decades, two imaging techniques, magnetic resonance elastography and transient elastography, have been developed and approved by the US Food and Drug Administration (FDA) for the assessment of hepatic fibrosis. Although high‐quality, psoriasis‐specific data are lacking, both methods have been shown to have outstanding efficacy in the detection of hepatic fibrosis, particularly the more advanced stages which may warrant the choice of a therapeutic alternative to methotrexate. Dermatologists should be aware of the availability of these tests and understand their limitations. Prospective studies in psoriasis and methotrexate management using these techniques are needed.

New Targets of Therapy in T-Cell Lymphomas

T-cell lymphomas (TCL) are characterized by poor response to chemotherapy and generally poor outcome. While molecular profiling has identified distinct biological subsets and therapeutic targets in B-cell lymphomas, the molecular characterization of TCL has been slower. Surface markers expressed on malignant T-cells, such as CD2, CD3, CD4, CD25, and CD52 were the first TCL-specific therapeutic targets to be discovered. However, the presence of these receptors on normal T-cells means that monoclonal antibody (mAb)- or immunotoxin (IT)-based therapy in TCL inevitably results in variable degrees of immunosuppression. Thus, although some mAbs/IT have significant activity in selected subsets of TCL, more specific agents that target signaling pathways preferentially activated in malignant T-cells are needed. One such novel class of agents is represented by the histone deacetylase (HDAC) inhibitors. These molecules selectively induce apoptosis in a variety of transformed cells, including malignant T-cells, both in vitro and in vivo. Several HDAC inhibitors have been studied in TCL with promising results, and have recently been approved for clinical use. Immunomodulatory drugs, such as interferons and Toll Receptor (TLR) agonists have significant clinical activity in TCL, and are particularly important in the treatment of primary cutaneous subtypes (CTCL). Although most classical cytotoxic drugs have limited efficacy against TCL, agents that inhibit purine and pyrimidine metabolism, known as nucleoside analogues, and novel antifolate drugs, such as pralatrexate, are highly active in TCL. With improved molecular profiling of TCL novel pharmacological agents with activity in TCL are now being discovered at an increasingly rapid pace. Clinical trials are in progress and these agents are being integrated in combination therapies for TCL, both in the relapsed/refractory setting as well as front line.

Extramedullary granulocytic sarcoma of the skin, mediastinum, and pericardium

A 27‐year‐old man, with a past history of developmental delay, presented on 18 November 2005 for the evaluation of an acute onset of multiple red–violaceous nodules on the head, neck, and trunk of 5 days’ duration. The patient had no associated fever, chills, weight loss, night sweats, chest pain, dyspnea, lymphadenopathy, or organomegaly. He had no previous history of malignancies. A biopsy indicated a diagnosis of leukemia cutis ( Fig. 1 ). His initial complete blood count (CBC) was within normal limits. The 2‐week follow‐up revealed enlargement of the previous lesions and the development of new lesions ( Fig. 2 ). By the third week, the patient had developed dyspnea, but with normal breath sounds and oxygen saturation. Chest computed tomography demonstrated a mediastinal mass measuring 16 × 5.2 cm and pericardial thickening ( Fig. 3 ). The diagnosis of granulocytic sarcoma of the skin lesion and mediastinal mass was established on the basis of immunohistochemical stains, with positivity to CD43 and Leders preparation and negativity to CD3, CD4, CD5, CD8, CD10, CD20, CD23, CD30, CD34, CD56, bcl‐1, terminal deoxynucleotidyl transferase (TdT), and granzyme. The bone marrow was negative for malignant cells. CBC and chemistry panel were all normal. Nevertheless, the patient experienced increased dyspnea and developed a pericardial effusion which required a pericardial window. Cytology of the pericardial fluid was consistent with granulocytic sarcoma. Once the diagnosis of granulocytic sarcoma was established, the patient started a regimen of cytarabine, daunorubicin, and etoposide. Despite this, the skin lesions and mediastinal mass showed minimal response. Repeat computed tomography showed a mediastinal mass measuring 14.5 × 4.4 cm. The patients respiratory status required intubation and, 2 weeks later, his family requested that he be withdrawn from life support.