Treatment of coexistent psoriasis and lupus erythematosus.

BACKGROUND: The coexistence of psoriasis and lupus erythematosus (LE) is rare. Anecdotal evidence suggests that anti-tumor necrosis factor alfa (TNF-α) agents may be efficacious in LE, although their use is commonly avoided in this disease because of concern for lupus flare. OBJECTIVE: We sought to describe the epidemiology, serologic findings, and therapeutic choices in patients with coexistent psoriasis/psoriatic arthritis and LE and to determine the risk of lupus flares with TNF-α inhibitors. METHODS: We performed a retrospective multicenter study of patients given the diagnoses of psoriasis (or psoriatic arthritis) and lupus erythematosus (systemic LE or cutaneous LE, including either subacute cutaneous LE or discoid LE) at 2 academic tertiary-care centers. RESULTS: A total of 96 patients with a mean age of 56 years was included. We report higher-than-expected rates of white race and psoriatic arthritis. One clinical lupus flare was observed in a patient receiving a TNF-α inhibitor, resulting in an incidence of 0.92% lupus flares per patient-year of TNF-α inhibitor use. LIMITATIONS: Retrospective chart review, small sample size, and limited documentation. CONCLUSION: Anti-TNF-α agents, ustekinumab, and abatacept may be valid treatment options for patients with concomitant LE and psoriasis. Clinical lupus flares in LE patients treated with TNF-α inhibitors were infrequent.

Repigmentation of hair following adalimumab therapy.

Repigmentation of canities, or age-related grey or white hair, is a rare occurrence. Generalized repigmentation of grey-white hair has been reported following inflammatory processes, and heterochromia (localized patches of hair repigmentation) is even more unusual, reported in association with medication use and malignancy. Tumor necrosis factor (TNF) inhibitors are increasingly utilized medications for inflammatory disorders, including psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Hair loss, or alopecia, has been described among the side effects of these medications, but changes in hair pigmentation in association with this class of drugs have not previously been reported. We describe a patient with hair repigmentation associated with adalimumab therapy.

Cutaneous lymphocytic thrombophilic (macular) arteritis: a distinct entity or an indolent (reparative) stage of cutaneous polyarteritis nodosa? Report of 2 cases of cutaneous arteritis and review of the literature.

Recently, 2 putatively novel clinicopathological entities, macular arteritis (MA) and lymphocytic thrombophilic arteritis (LTA), have been described. Both exhibit an indolent chronic course and erythematous and hyperpigmented macules (MA > LTA) and papules/plaques (LTA > MA), often in a reticulated pattern on the lower limbs. Histopathologically, they show varying degrees of lymphocyte infiltration and disruption of the arterial wall, concentric luminal fibrin deposition, and in some cases, fibrointimal scarring (endarteritis obliterans). This spectrum of histology overlaps with the subacute, reparative, and healed stages reported for cutaneous polyarteritis nodosa (CPAN). Herein, we report 2 cases of cutaneous lymphocytic arteritis, 1 with persistent indolent disease and the second with acute self-limited disease. Comparing these 2 patients' findings with that reported for MA, LTA, and CPAN highlights a clinicopathologic spectrum, which exhibits increasing disease severity moving from MA to LTA to CPAN to systemic polyarteritis nodosa. Given the clinicopathologic similarities, we conclude that our cases and cases previously reported as MA or LTA likely represent an indolent form of CPAN.

Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly T(H)2/"T22" immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate-to-severe AD. In patients with psoriasis, NB-UVB has been found to suppress T(H)1/T(H)17 polarization, with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in patients with AD. OBJECTIVE: We sought to evaluate the effects of NB-UVB on immune and barrier abnormalities in patients with AD, aiming to establish reversibility of disease and biomarkers of therapeutic response. METHODS: Twelve patients with moderate-to-severe chronic AD received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and nonlesional skin biopsy specimens were obtained before and after treatment and evaluated by using gene expression and immunohistochemistry studies. RESULTS: All patients had at least a 50% reduction in SCORAD index scores with NB-UVB phototherapy. The T(H)2, T22, and T(H)1 immune pathways were suppressed, and measures of epidermal hyperplasia and differentiation normalized. The reversal of disease activity was associated with elimination of inflammatory leukocytes and T(H)2/T22- associated cytokines and chemokines and normalized expression of barrier proteins. CONCLUSIONS: Our study shows that resolution of clinical disease in patients with chronic AD is accompanied by reversal of both the epidermal defects and the underlying immune activation. We have defined a set of biomarkers of disease response that associate resolved T(H)2 and T22 inflammation in patients with chronic AD with reversal of barrier pathology. By showing reversal of the AD epidermal phenotype with a broad immune-targeted therapy, our data argue against a fixed genetic phenotype.

Lesional dendritic cells in patients with chronic atopic dermatitis and psoriasis exhibit parallel ability to activate T-cell subsets.

BACKGROUND: Atopic dermatitis (AD) and psoriasis represent polar immune diseases. AD is a T(H)2/T(H)22-dominant disease, whereas psoriasis is considered a T(H)1/T(H)17 disease. Local immune deviation is suggested to be regulated by dendritic cell (DC)-induced T-cell polarization and recruitment of specific T-cell subsets by chemokines. Although the role of chemokines is well documented, the actual contribution of DCs to activate polar T-cell subsets in human subjects is still a matter of speculation. OBJECTIVE: We sought to elucidate the significance of each cutaneous DC subset in disease-specific T-cell immune deviation. METHODS: We performed a comprehensive analysis of major cutaneous resident (Langerhans cells and blood dendritic cell antigen 1-positive dermal DCs) and inflammatory (inflammatory dendritic epidermal cells and blood dendritic cell antigen 1-negative dermal DCs) DC subsets directly isolated from the lesional skin of patients with AD and those with psoriasis. RESULTS: The ability of each DC subset to expand T(H)1, T(H)2, T(H)17, and T(H)22 subsets was similar between the 2 diseases, despite the association of both with accumulation of resident and inflammatory DCs. We also confirmed differential upregulation of chemokine expression in patients with AD (CCL17, CCL18, and CCL22) and psoriasis (CXCL1, IL-8, and CCL20). The expression of CCL17 and CCL22 was higher in Langerhans cells from patients with AD than from patients with psoriasis, whereas the opposite was observed for CXCL9 and CXCL10. CONCLUSION: Our results suggest that DC polarity does not directly drive differential T-cell subset responses. Alternatively, disease-specific chemokines might recruit specific memory T-cell subsets into the skin, which in turn might be activated and expanded by DCs at the site of inflammation, maintaining differential immune polarity in these diseases.

Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease with a T(H)2 and "T22" immune polarity. Despite recent data showing a genetic predisposition to epidermal barrier defects in some patients, a fundamental debate still exists regarding the role of barrier abnormalities versus immune responses in initiating the disease. An extensive study of nonlesional AD (ANL) skin is necessary to explore whether there is an intrinsic predisposition to barrier abnormalities, background immune activation, or both in patients with AD. OBJECTIVE: We sought to characterize ANL skin by determining whether epidermal differentiation and immune abnormalities that characterize lesional AD (AL) skin are also reflected in ANL skin. METHODS: We performed genomic and histologic profiling of both ANL and AL skin lesions (n = 12 each) compared with normal human skin (n = 10). RESULTS: We found that ANL skin is clearly distinct from normal skin with respect to terminal differentiation and some immune abnormalities and that it has a cutaneous expansion of T cells. We also showed that ANL skin has a variable immune phenotype, which is largely determined by disease extent and severity. Whereas broad terminal differentiation abnormalities were largely similar between involved and uninvolved AD skin, perhaps accounting for the "background skin phenotype," increased expression of immune-related genes was among the most obvious differences between AL and ANL skin, potentially reflecting the "clinical disease phenotype." CONCLUSION: Our study implies that systemic immune activation might play a role in alteration of the normal epidermal phenotype, as suggested by the high correlation in expression of immune genes in ANL skin with the disease severity index.

MYC Amplification in Epithelioid Angiosarcoma of the Urinary Bladder and Prostate Following Prostate Radiotherapy: A Case Report with a Novel Molecular Alteration.

Epithelioid angiosarcoma is a rare variant of angiosarcoma. Radiation-associated epithelioid angiosarcoma of the urinary bladder and prostate is an exceedingly rare tumor and there are only 8 cases of epithelioid angiosarcoma of the urinary bladder and prostate associated with previous radiotherapy in the literature. To the best of our knowledge, MYC gene amplification has not been previously reported in epithelioid angiosarcoma of the urinary bladder and prostate following radiotherapy, although it is observed in radiation-associated angiosarcoma of other anatomic sites. Here we report the first case of epithelioid angiosarcoma of the urinary bladder and prostate with MYC gene amplification detected by fluorescence in situ hybridization (FISH) analysis in a 70-year-old male patient 10 years after receiving radiation and hormonal therapy for prostate cancer.

Classic Findings, Mimickers, and Distinguishing Features in Primary Blistering Skin Disease.

CONTEXT.­: Blistering diseases comprise a large group of clinically polymorphic and sometimes devastating diseases. During the past few decades, we have developed an elegant understanding of the broad variety of blistering diseases and the specific histopathologic mechanism of each. OBJECTIVE.­: To review examples of the classic findings of specific blistering diseases and emphasize the importance of considering unrelated conditions that can mimic the classic finding. DATA SOURCES.­: This article combines data from expert review, the medical literature, and dermatology and pathology texts. CONCLUSIONS.­: We have chosen several common examples of classic blistering diseases that are mimicked by other cutaneous conditions to highlight the basic findings in blistering conditions and the importance of clinician-to-pathologist communication.

Psoriatic arthritis for the dermatologist.

Psoriatic arthritis (PsA) is a chronic, progressive, inflammatory spondyloarthropathy that affects approximately one-third of patients with all types of psoriasis. Dermatologists are in a unique position to recognize early symptoms of PsA, initiate appropriate therapy, and prevent development of further disability. The course of PsA can be modulated by immunosuppressive therapy; patients with moderate-to-severe disease require aggressive management with medications proven to halt disease progression. It is essential for the dermatologist to understand the safety, tolerability, efficacy, cost, and potential to halt disease progression with available medications for this relatively common and potentially disabling disease.

Apremilast for the treatment of psoriatic arthritis.

Psoriatic arthritis occurs in about one-third of patients with psoriasis, and is a severely disabling, progressive inflammatory spondyloarthropathy typically treated with non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, TNF-α inhibitors and ustekinumab. These medications moderately improve the arthritis, dactylitis, and enthesitis that characterize psoriatic arthritis, however, they are associated with serious long-term adverse effects, issues with safety and tolerability, and high cost. Moreover, many patients do not respond or have resistant or recurrent manifestations to these agents. Apremilast is an orally available phosphodiesterase type 4 inhibitor that may block the pathogenic inflammatory Th17 and Th1 pathways upstream of current biologics, which target extracellular molecules of the immunological response.

Cutaneous porphyrias part II: treatment strategies.

The porphyrias are diverse in pathophysiology, clinical presentation, severity, and prognosis, presenting a diagnostic and therapeutic challenge. Although not easily curable, the dermatological manifestations of these diseases, photosensitivity and associated cutaneous pathology, can be effectively prevented and managed. Sun avoidance is essential, and patient education regarding the irreversibility of photocutaneous damage is a necessary corollary. Beyond preventative measures, the care of fragile, vulnerable skin, and pain management, each of the porphyrias has a limited number of unique additional therapeutic options. Many of the treatments have been published only in small case series or anecdotal reports and do not have well-understood nor proven mechanisms of action. This article presents a comprehensive review of available therapeutic options and long-term management recommendations for the cutaneous porphyrias.

Cutaneous porphyrias part I: epidemiology, pathogenesis, presentation, diagnosis, and histopathology.

The porphyrias are a group of disorders characterized by defects in the heme biosynthesis pathway. Many present with skin findings including photosensitivity, bullae, hypertrichosis, and scarring. Systemic symptoms may include abdominal pain, neuropsychiatric changes, anemia, and liver disease. With advances in DNA analysis, researchers are discovering the underlying genetic causes of the porphyrias, enabling family members to be tested for genetic mutations. Here we present a comprehensive review of porphyria focusing on those with cutaneous manifestations. In Part I, we have included the epidemiology, pathogenesis, presentation, diagnosis, and histopathology. Treatment and management options will be discussed in Part II.