Bruce H. Thiers

Immunological profiles in alopecia areata

Cell‐mediated immunity and auto‐immune phenomena were investigated in sixty patients with active alopecia areata of various degrees of severity. Serum auto‐antibodies to thyroid antigens were detected in twenty‐three patients. Examination of T‐lymphocyte populations, lymphocyte DNA synthesis, and lymphokine production in response to mitogen stimulation revealed no differences between the sixty patients and matched healthy control subjects. However, patients with thyroid auto‐immunity and/or the presence of alopecia totalis or universalis showed significant reductions in interactive T lymphocytes (recognized by rosette formation with human B lymphoblastoid cells) and diminished production of leukocyte migration inhibition factor in response to stimulation with phytohaemagglutinin. This suggests that immune mechanisms may be involved in the pathogenesis of alopecia areata which is associated with thyroid auto‐immunity or which progresses to total hair loss.

Controversies in mycosis fungoides

Most clinicians agree that mycosis fungoides is the prototypic cutaneous T cell lymphoma. However, certain clinical characteristics indicate that this disorder may begin as a reactive rather than a neoplastic process. The concept of a nonneoplastic etiopathogenesis of mycosis fungoides is further supported by recent data on the function of Langerhans cells, a population of epidermal cells known to play a critical role in immune surveillance and the development of contact sensitivity. It has been suggested that chronic occupational exposure to environmental allergens results in persistent antigenic stimulation, leading to a breakdown in immune surveillance and eventually, malignancy. Modern laboratory technics have enhanced the clinicians ability to diagnose and stage mycosis fungoides. Data obtained from such studies have indicated that systemic spread may occur much earlier in the course of disease than has previously been appreciated. The therapeutic implications of such knowledge are as yet uncertain.

Cutaneous blastomycosis: a diagnostic challenge

Primary cutaneous inoculation blastomycosis occurs less commonly than secondary blastomycosis, in which cutaneous lesions most often originate from a primary pulmonary infection which disseminates through the blood or lymphatics to involve the skin. In secondary cutaneous blastomycosis, the primary pulmonary infection is frequently subclinical at the time cutaneous lesions manifest. Here we report two cases that illustrate the difficulty in distinguishing between primary and secondary cutaneous involvement. We also review the expanding literature on blastomycosis since its identification over a century ago.

An open-label trial of immunomodulation therapy with inosiplex (Isoprinosine) in patients with alopecia totalis and cell-mediated immunodeficiency

Nine patients with alopecia totalis and associated defects in T lymphocyte function were admitted to an open-label trial of inosiplex therapy. All nine developed enhanced T cell function and seven had clinically significant hair regrowth. The immunologic response to inosiplex was dose-dependent in five patients. These data provide new information on the in vivo effects of inosiplex on the human immune system and support the hypothesis that disturbances of immunologic mechanisms may play a pathogenetic role in alopecia totalis in certain patients.

Cutaneous T-cell lymphoma

Cutaneous T‐cell lymphoma (CTCL) is a neoplasm of helper T cells whose first manifestations usually appear in the skin. The various forms of CTCL are distinguished by both clinical features and histopathology. Early on, the diagnosis may be difficult to establish because of its numerous, and often non‐specific, clinical presentations. Further, the pathological findings of early lesions may lack the diagnostic features observed in well‐developed or advanced disease. The diagnosis of CTCL must be considered in any patient with a chronic, therapy‐resistant condition of the skin. In patients with non‐specific histological findings, a high index of suspicion and multiple biopsies may eventually lead to a diagnosis of CTCL. Once the diagnosis of CTCL is established, accurate staging is essential both for its effect on treatment decisions and for its prognostic value. In general, CTCL is a chronic, slowly progressive disease with a long evolution. The development of tumours is a poor prognostic sign, as is erythroderma. The Sezary syndrome is a distinct form of erythrodermic CTCL that is characterized by exfoliative erythroderma, lymphadenopathy, lymphocytosis, intense pruritus, and circulating large, abnormal lymphocytes (Sezary cells). When death does occur, it is most often due to septicemia. Treatment of CTCL must be tailored to the individual patient. The most commonly employed treatment options are photochemotherapy and topical chemotherapy.

Chemokine receptor expression in non‐melanoma skin cancer

Background:  Previous studies suggest that chemokines and chemokine receptors have a role in the metastatic process. A correlation exists between the specific expression of these chemoattractive, pro‐inflammatory cytokines and the ability of cancer to disseminate. Prior studies have shown that in metastatic melanoma and squamous cell carcinoma of the head and neck upregulation of CXC (α) chemokine receptor (CXCR)4 and CC (β) chemokine receptor (CCR)7 expression is accompanied by downregulation of the chemokine receptor CCR6. However, the expression patterns of CCR6, CCR7 and CXCR4 in non‐melanoma skin cancer have yet to be elucidated.

Automatic diagnosis of melanoma using machine learning methods on a spectroscopic system

BackgroundEarly and accurate diagnosis of melanoma, the deadliest type of skin cancer, has the potential to reduce morbidity and mortality rate. However, early diagnosis of melanoma is not trivial even for experienced dermatologists, as it needs sampling and laboratory tests which can be extremely complex and subjective. The accuracy of clinical diagnosis of melanoma is also an issue especially in distinguishing between melanoma and mole. To solve these problems, this paper presents an approach that makes non-subjective judgements based on quantitative measures for automatic diagnosis of melanoma.MethodsOur approach involves image acquisition, image processing, feature extraction, and classification. 187 images (19 malignant melanoma and 168 benign lesions) were collected in a clinic by a spectroscopic device that combines single-scattered, polarized light spectroscopy with multiple-scattered, un-polarized light spectroscopy. After noise reduction and image normalization, features were extracted based on statistical measurements (i.e. mean, standard deviation, mean absolute deviation, L1 norm, and L2 norm) of image pixel intensities to characterize the pattern of melanoma. Finally, these features were fed into certain classifiers to train learning models for classification.ResultsWe adopted three classifiers – artificial neural network, naïve bayes, and k-nearest neighbour to evaluate our approach separately. The naive bayes classifier achieved the best performance - 89% accuracy, 89% sensitivity and 89% specificity, which was integrated with our approach in a desktop application running on the spectroscopic system for diagnosis of melanoma.ConclusionsOur work has two strengths. (1) We have used single scattered polarized light spectroscopy and multiple scattered unpolarized light spectroscopy to decipher the multilayered characteristics of human skin. (2) Our approach does not need image segmentation, as we directly probe tiny spots in the lesion skin and the image scans do not involve background skin. The desktop application for automatic diagnosis of melanoma can help dermatologists get a non-subjective second opinion for their diagnosis decision.

Making proper judgement when choosing a treatment for actinic keratosis

Actinic keratosis is a complex clinical disease for which no clear method exists to predict whether a given lesion will regress, remain stable or progress to non-melanoma skin cancer. Treating all (including subclinical) lesions with field-directed therapy to lower the risk of malignant transformation has been an important evolution in actinic keratosis management. In selected patients, lesion-directed approaches continue to occupy an important role. Despite the associated issues, cryotherapy remains standard of care. Early evidence with a new topical lesion-directed treatment containing low-dose-5-fluorouracil 0.5%/salicylic acid 10% suggests relevant advantages over cryotherapy in terms of sustained lesion clearance. For a condition with such a high global prevalence, remarkably little is known about the economic burden of actinic keratosis and relative cost–effectiveness of the various treatment modalities. Several questions need to be addressed if the challenges of increasing numbers of cases in years...

Dermatologic drug use during pregnancy and lactation

Physicians are often asked to prescribe medication for women during the childbearing years. This article reviews which dermatologic drugs have been reported to interfere with contraceptive efficacy, which should be avoided, and which have the fewest contraindications for use during pregnancy and lactation. Corticosteroids and tretinoin are discussed in detail. Sources and guidelines for choices of dermatologic drugs for women of childbearing age are presented.

Physician drug dispensing

We have reviewed the issue of physician drug dispensing by focusing upon quality of care, economic considerations, drug availability, patient compliance, safety, and increased governmental regulation. From a quality of care perspective, the increased use of pharmacist assistants, the tendency toward generic and therapeutic drug substitution, and the less specialized clinical education of pharmacists all pose hazards rather than safety checks upon physician prescribing. There is no evidence that pharmacists charge less than physicians. If they did, there would be no need to protect their incomes legislatively by restricting physician dispensing. Economic motivation per se is less important to a physician than providing a true convenience for his patients and thus encouraging a closer doctor-patient relationship. Physician dispensing adds to the availability of medication and may minimize the number of patients shuttling between pharmacies to obtain complex multi-ingredient preparations. Compliance is enhanced as availability increases. Prepackaged pharmaceuticals prepared under the auspices of pharmacists and dispensed by physicians are at least as safe as those prepared by the ungloved hands of a pharmacist hidden behind store counters. Thus, restricting the physicians right to dispense can negatively affect the quality of medical care, the cost of medications, safety, the availability of pharmaceuticals, and patient compliance. Such limitation is certainly not in the best interest of our patients.