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Brentuximab vedotin is a CD30-antibody/drug conjugate which has demonstrated excellent response in treating CD30-positive mycosis fungoides (MF) and anaplastic large cell lymphoma (ALCL). In this report, we present a patient with CD30-negative MF refractory to multiple other lines of therapy who demonstrated a dramatic response to brentuximab. This paradoxical response may be due to inadequate detection of CD30 expression by immunohistochemical techniques. From this case we see that even in the setting of apparent CD30 negativity, brentuximab may be a viable treatment option for patients who require bridging to stem cell transplant or seek successful palliation. This case highlights the point that rigid inclusion criteria for MF trials without use of more sensitive techniques to confirm lack of CD30 expression may inappropriate.

New drug treatment opportunities based on the results of a genome-wide association study, which implicate T cell and natural killer (NK)-cell activation pathways, are leading to new approaches in future clinical trials of alopecia areata. Special attention is being given to the UL 16-binding protein (ULBP3) gene cluster on chromosome 6q25, as these genes make the NKG2D-activating ligand or signal that can trigger the NKG2D receptor, initiating an autoimmune response. A greater expression of ULBP3 has also been found in hair follicles in scalp biopsy specimens from patients with active disease. It is now postulated that the characteristic T cell "swarm of bees" infiltrate seen in alopecia areata is the result of T cells being attracted to the hair follicle by NKG2D-activating ligands. Future treatment approaches for alopecia areata include use of drugs that: (i) block the NKGD-activating ligand and NKG2D receptor interaction, (ii) halt activated T cells, or (iii) modification of the inflammatory cytokine network. Many drugs currently being used or being evaluated for other autoimmune diseases that work through these mechanisms might prove to be very effective in alopecia areata.

Alopecia areata (AA) may can occur on any hair-bearing region. Patients can develop patchy nonscarring hair loss or extensive loss of all body hair. Hair loss may fluctuate. Some patients experience recurrent hair loss followed by hair regrowth, whereas others may only develop a single patch of hair loss, never to see the disease again. Still others experience extensive loss of body hair. The heterogeneity of clinical presentations has led investigators conducting clinical therapeutic trials to typically group patients into three major groups, those with extensive scalp hair loss [alopecia totalis (AT)], extensive body hair loss [alopecia universalis (AU)], or patchy disease (AA). Treatment outcomes have been correlated with disease duration and extent. Recently, guidelines were established for selecting and assessing subjects for both clinical and laboratory studies of AA, thereby facilitating collaboration, comparison of data, and the sharing of patient-derived tissue. For reporting purposes the terms AT and AU, though still used are defined very narrowly. AT is 100% terminal scalp hair loss without any body hair loss and AU is 100% terminal scalp hair and body loss. AT/AU is the term now recommended to define the presence of AT with variable amounts of body hair loss. In this report the term AA will be used broadly to encompass the many presentations of this disease. Development of AA may occur with changes in other ectodermal-derived structures such as fingernails and toenails. Some investigators have also suggested that other ectodermal-derived appendages as sebaceous glands and sweat glands may be affected in patients experiencing AA. Whether or not function of these glands is truly impaired remains to be confirmed. Many patients who develop patchy or extensive AA complain of changes in cutaneous sensation, that is, burning, itching, tingling, with the development of their disease. Similar symptoms may occur with hair regrowth. The potential involvement of the nervous system in AA has led to morphologic investigations of the peripheral nervous system as well as analysis of circulating neuropeptide levels. In this article the clinical presentations of AA are reviewed. The guidelines for conducting treatment studies of AA are presented and observations on changes in cutaneous innervation are introduced. Throughout the text, unless otherwise noted, AA will be used in a general way to denote the spectrum of this disease.

Alopecia areata (AA) patients show a variable response in hair regrowth with glucocorticoid (GC) steroid treatment. The biochemical mechanisms by which GCs stimulate hair growth in patients with AA is unknown, yet clinicians commonly use topical, intralesional, and even oral GC steroid therapy to treat AA. In this study, scalp biopsy specimens were obtained from 15 patients (in each group) with extensive AA, male androgenetic alopecia (AGA), and normal controls (N), and were analyzed for GC receptor (GCR) content. All patients were off therapy at the time they were studied. Tissue samples were assessed for total, occupied, and unoccupied GCR type I and II binding. Results from patients with AA show that the type II GCR is elevated and in an unoccupied state compared to AGA and N patient biopsies (p < 0.01). A factor known to activate the GCR, called thioredoxin (TR), was decreased in AA scalp compared to N and AGA (p < 0.01). Finding elevated unoccupied type II GCR with diminished TR levels indicates inhibition of cellular transcription. This may be important in explaining the variable responses seen with GC treatment for hair regrowth in patients with AA and gives the clinician possible reasons why steroids may not always be effective in treating this difficult hair disease.

New drug treatment opportunities based on the results of a genome-wide association study, which implicate T cell and natural killer (NK)-cell activation pathways, are leading to new approaches in future clinical trials of alopecia areata. Special attention is being given to the UL 16-binding protein (ULBP3) gene cluster on chromosome 6q25, as these genes make the NKG2D-activating ligand or signal that can trigger the NKG2D receptor, initiating an autoimmune response. A greater expression of ULBP3 has also been found in hair follicles in scalp biopsy specimens from patients with active disease. It is now postulated that the characteristic T cell "swarm of bees" infiltrate seen in alopecia areata is the result of T cells being attracted to the hair follicle by NKG2D-activating ligands. Future treatment approaches for alopecia areata include use of drugs that: (i) block the NKGD-activating ligand and NKG2D receptor interaction, (ii) halt activated T cells, or (iii) modification of the inflammatory cytokine network. Many drugs currently being used or being evaluated for other autoimmune diseases that work through these mechanisms might prove to be very effective in alopecia areata.

Chronic cutaneous lupus erythematosus consists of three major dermatologic diseases: discoid lupus erythematosus (DLE), lupus panniculitis/lupus profundus, and lupus tumidus (Table 1). DLE is estimated to be responsible for 50-85% of patients with chronic cutaneous lupus erythematosus. Scalp involvement is most often the presenting symptom. The clinical features and diagnosis of DLE, its pathophysiology and treatment, are reviewed.