Drug survival of biologic therapy in a large, disease-based registry of patients with psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

BACKGROUND: Drug survival is a marker for treatment sustainability in chronic diseases such as psoriasis. OBJECTIVE: The aim of these analyses was to assess survival of biologic treatments in the PSOriasis Longitudinal Assessment and Registry (PSOLAR). METHODS: PSOLAR is a large, prospective, international, disease-based registry of patients with psoriasis receiving (or eligible for) systemic therapy in a real-world setting. Drug survival is defined as the time from initiation to discontinuation (stop/switch) of biologic therapy on registry. The number of patients who discontinued each treatment and the duration of therapy were recorded. Using Kaplan-Meier survival curves and Cox-regression analyses [hazard ratios (HR) and 95% confidence intervals (CIs)], time to discontinuation was compared across cohorts undergoing first-, second- or third-line treatment with ustekinumab, infliximab, adalimumab or etanercept. RESULTS: As of the 2013 data cut, 12 095 patients with psoriasis were enrolled in PSOLAR. Of the 4000 patients initiating any new biologic therapy, approximately 3500 started a first-line, second-line or third-line biologic therapy during the registry. Lack of effectiveness was the most common reason for discontinuation across biologic therapies. Based on the multivariate analysis, significantly shorter times to discontinuation were observed for infliximab [HR (95%CI) = 2.73 (1.48-5.04), P = 0.0014]; adalimumab [4.16 (2.80-6.20), P < 0.0001]; and etanercept [4.91 (3.28-7.35) P < 0.0001] compared with ustekinumab [reference treatment]) for first-line biologic use; results were similar for treatment effects for second/third-line therapies. Although limited in power, analyses in patients with concurrent psoriatic arthritis confirmed by a rheumatologist reflect observations in the overall psoriasis population. CONCLUSION: Drug survival was superior for ustekinumab compared with infliximab, adalimumab and etanercept in patients with psoriasis.

[Type I cryoglobulinemia with a fatal outcome]. / Crioglobulinemia tipo I de desenlace fatal.

Type I cryoglobulinemia, a condition associated with lymphoproliferative disorders, is caused by monoclonal immunoglobulins that precipitate at low temperatures. It mostly involves the skin and pathology study shows no signs of vasculitis. Management is usually based on immunosuppressive drugs associated with plasmapheresis for severe disease. The use of rituximab has recently been described for resistant cases. We present an unusual case of long-standing type I cryoglobulinemia associated with a monoclonal gammopathy of unknown significance. The patient developed extremely severe skin lesions with histological signs of vasculitis. The patient died due to the onset of noncutaneous manifestations of the cryoglobulinemia and complications of the immunosuppressive treatment.

Biological agents in the treatment of psoriasis.

Psoriasis is a chronic immune-mediated inflammatory disease, with an estimated prevalence of 1-3% worldwide. It is considered to be a multisystemic disorder, primarily affecting the skin and joints (psoriatic arthritis), and associated with other inflammatory conditions such as inflammatory bowel disease and coronary heart disease among others. Today, thanks to recent scientific advances that have allowed us to deepen our understanding of the pathogenesis of psoriasis, we count with an expanded therapeutic armamentarium that includes targeted therapy in the form of ''biologics''. These agents have gained popularity as safe, effective, and convenient alternatives for the treatment of chronic moderate to severe plaque psoriasis. This review will focus on the main biologics used in the treatment of moderate to severe plaque psoriasis: efalizumab, alefacept, etanercept, infliximab, adalimumab and the new Interleukin (IL) 12/23 inhibitors.

Immunohistochemical evaluation of toxic epidermal necrolysis treated with human intravenous immunoglobulin.

AIM: Toxic epidermal necrolysis (TEN) is a severe drug reaction characterized by massive epidermal cell death. The authors of the current study and others have noted improved outcomes in TEN patients treated with human intravenous immunoglobulin (IVIG), purportedly due to its ability to inhibit the fas/fas-ligand (Fas-L) apoptotic pathway, but published case series evaluating TEN through the use of immunohistochemical antibody stains for Fas and Fas-L before and after IVIG treatment are lacking. The authors hypothesized that due to IVIG's ability to arrest the evolution of TEN, expression of Fas/Fas-L on keratinocytes would be decreased or absent following IVIG treatment. METHODS: Ten patients diagnosed with TEN underwent biopsies of their lesions prior to and five days after treatment with IVIG. Seven post-treatment biopsies were of sufficient quality to undergo evaluation. RESULTS: All ten pretreatment biopsies had Fas and Fas-L expression by immunohistochemistry, while six out of seven (85.7%) post-treatment biopsies failed to demonstrate Fas or Fas-L expression. One of seven post-treatment biopsies stained positive for Fas and Fas-L. CONCLUSION: This reduced immunohistochemical expression of apoptotic markers may represent IVIG inhibition of the pathogenic mechanism of TEN. Alternatively reduced Fas and Fas-L may be a feature of reepithelialization in TEN, or characteristic of rapidly proliferating epidermis.

Infliximab monotherapy in psoriasis: a case of rapid clinical and histological response.

BACKGROUND: Psoriasis is a common chronic relapsing, inflammatory, hyperproliferative skin disorder with genetic predisposition. There is currently no experimental model for psoriasis and the pathogenesis is not fully understood. Psoriatic plaques have been shown to contain increased levels of cytokines, including tumor necrosis factor alpha (TNF-alpha). Anti-tumor necrosis factor therapy with infliximab has been shown to be highly effective in recalcitrant psoriasis. METHODS: We evaluated the efficacy and timeline of histological changes in a psoriatic plaque following infliximab infusion. A patient with severe recalcitrant plaque psoriasis was clinically and histologically assessed for improvement. RESULTS: We found rapid clinical improvement with infliximab accompanied by histopathological changes. The earliest effects were seen on neutrophils and lymphocytes whereas keratinocyte normalization was not evident at the early stages. CONCLUSION: Infliximab is not only an effective agent in the treatment of psoriasis but appears to have a very rapid onset of action.

Infliximab for hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic disease characterized by significant morbidity. Current medical therapies are only minimally effective at treating the disease. Infliximab is a chimeric monoclonal antibody with high affinity for tumour necrosis factor (TNF)-alpha. TNF-alpha is known to induce proinflammatory cytokines and may play an important role in the therapy of a number of disparate inflammatory disorders. Infliximab has shown promise for the therapy of rheumatoid arthritis and psoriasis. OBJECTIVES: Retrospectively to evaluate the effectiveness of infliximab for the treatment of HS. METHODS: A retrospective chart review was performed for patients who received infliximab at the University of Miami Department of Dermatology. Patients were contacted and asked retrospectively to rate their disease activity immediately prior to and after therapy. RESULTS: Patients' self-reported disease activity scores were significantly decreased (P = 0.0001, paired t-test) following infliximab infusion. This correlated with physician-observed clinical improvement. CONCLUSIONS: Infliximab is a promising agent for the treatment of HS. These initial results suggest that infliximab is associated with objective and subjective improvement in HS. Further controlled studies of the efficacy of infliximab and its effect on the course of the disease are warranted.

Inpatient dermatology. A prescription for survival.

Currently, only a minority of dermatologists participate in the primary hospital care of patients with severe skin disease. However, an opportunity exists to alter this course. We believe the current course is a detriment to our specialty, and as a specialists we should provide the care for the full spectrum of dermatologic diseases. Moreover, by not delivering complete dermatology care, our specialty also stands to lose respect from both our patients and peers. Our experience at UM suggests that the creation of a cadre of dermatology hospitalists at selected academic medical centers would allow improved patient hospital care, education, and research.

Toxic epidermal necrolysis of the scalp following anticonvulsant use and cranial irradiation.

BACKGROUND: Toxic epidermal necrolysis (TEN) of the scalp is rare but it has been shown to occur in patients who had been given a combination of cranial radiation and anticonvulsant therapies. OBJECTIVE: We present a 62-year-old man who received cranial irradiation following craniotomy for glioblastoma multiforme. After he was prescribed the anticonvulsant phenytoin for postsurgical seizure prophylaxis, the patient developed TEN which began on the scalp before spreading to involve other parts of his body. Our second case was a 55-year-old woman who had been diagnosed with lung carcinoma with metastasis to the brain. She was treated with cranial irradiation and the anticonvulsant carbamazepine. TEN developed first on the scalp and then became generalized. CONCLUSIONS: While the combination of radiation and anticonvulsants leads to an increased risk of developing TEN, cranial irradiation appears to be the localizing factor in the development of TEN of the scalp.

Immunoablative high-dose cyclophosphamide without stem cell rescue in a patient with pemphigus vulgaris.

The use of ablative intravenous cyclophosphamide (50 mg/kg per day for 4 days) without stem cell rescue has been described in patients with refractory autoimmune diseases such as paraneoplastic pemphigus, systemic lupus erythematosus, and aplastic anemia. We describe a 33-year-old patient with pemphigus vulgaris recalcitrant to multiple therapies. The patient presented with numerous oral ulcerations, erosions, and hyperpigmented crusted plaques on his face, trunk, and arms. Findings of a skin biopsy and direct immunofluorescence were consistent with pemphigus vulgaris. The circulating pemphigus vulgaris autoantibodies were present at a titer of 1:640. The patient received immunoablative therapy (50 mg/kg of cyclophosphamide for a total of 4 days) and tolerated the regimen well. Complications such as thrombocytopenia and Pseudomonas septicemia were quickly treated. Four months after the 4-day therapy, his oral and skin lesions completely healed, and his pemphigus titers have decreased to zero. He is no longer receiving prednisone and no new lesions have developed. This provides further evidence that this regimen is relatively safe and provides a potential "cure" for refractory autoimmune diseases such as pemphigus vulgaris.

Sustained improvement of the quality of life of patients with psoriasis after hospitalization.

Psoriasis is a chronic, recurrent, and often disfiguring skin disease that may significantly affect patients' quality of life. Treatment of psoriasis, including hospitalization, has been shown to improve quality of life. A pilot study of 15 consecutive inpatients and 7 consecutive outpatients with psoriasis were asked to complete the Dermatology Life Quality Index (DLQI) before treatment and 3 months later. Hospitalized patients also completed the DLQI 1 week after discharge. Statistical analysis using t tests compared pretreatment and posttreatment DLQI scores as well as improvement of inpatients versus outpatients. Baseline DLQI scores for hospitalized patients were significantly higher (greater impairment of life quality) compared with oupatients' quality of life. After discharge, hospitalized patients' quality of life had significantly improved at 1 week and remained improved at 3 months.

Performance comparison of nylon and an absorbable suture material (Polyglactin 910) in the closure of punch biopsy sites.

The ability to close biopsy sites primarily without the need for removing sutures is obvious. However, it was unclear whether absorbable sutures could be used for this purpose. We prospectively studied 10 healthy volunteers on whom one 3 mm punch biopsy was performed on each arm. In each subject two sutures were compared for closure of the biopsy sites, polyglactin 910 and nylon. Our primary goal was to compare absorbable and nonabsorbable sutures in the closure of punch biopsy sites. Each site was closed with one simple percutaneous suture. The sites were evaluated at 2 weeks and 6 months for redness, infection, dehiscence, scar hypertrophy, and patient satisfaction. We found no statistically significant difference between the two suture materials in any of the above parameters. Therefore we conclude that absorbable sutures are a good alternative in the primary closure of skin biopsy sites.

Inpatient dermatology. The difficulties, the reality, and the future.

Changes in the health care delivery system have profoundly affected medical dermatology in the United States. Although a significant number of patients are still being admitted for skin and skin-related disorders, only a minority are now admitted by dermatologists. An analysis of the mechanics of such a change and a national perspective is presented.

The effect of health care delivery systems on admission to and treatment at an inpatient dermatology unit.

The University of Miami Department of Dermatology has maintained an active inpatient unit. Analysis of data from a 12 month period from 1995-1996 showed 562 admissions. Cutaneous lymphoma, psoriasis, and chronic wounds accounted for over half the admissions. Most patients were insured by a fee-for-service system, and compared to patients insured by managed care systems or patients who were indigent, fee-for-service patients had the shortest length of stay. Using a case mix severity index, indigent patients had the greatest disease severity followed by fee-for-service patients. Patients enrolled in managed care systems had the least severity suggesting that factors other than disease severity alone may play a role in determining why patients are admitted.

Other novel immunosuppressants.

The use of immunosuppressive agents in dermatology has increased widely. The role of these medications has become increasingly important for the treatment of dermatologic disorders in an inpatient setting, where there is frequently a requirement for highly potent, fast-acting, effective agents. This article presents an overview of the general application, mechanisms of action, metabolism, and adverse effects commonly associated with systemic immunosuppressive agents used in dermatology.

Dermatologic disease accounts for a large number of hospital admissions annually.

BACKGROUND: Severe skin disease uncommonly requires hospitalization. The number of patients hospitalized for skin disease annually in the United States has never been reported. OBJECTIVE: We evaluated the number of patients admitted for skin disorders. METHOD: Using data from 2 national databases, the Healthcare Cost and Utilization Project-3 Nationwide Inpatient Sample (HCUP-3 NIS) 1992-1994 and Medicare Provider Analysis and Review (MEDPAR) 1990-1996 file, we evaluated the total discharges, total charges, and reimbursement of the dermatology-specific (272, 273, 283, and 284) and -related (263, 264, 265, 266, 271, 277, 278, and 279) diagnosis-related groups (DRGs). RESULTS: In 1994, the HCUP-3 NIS data showed that a total of 468,014 discharges were classified under Dermatology DRGs, whereas in 1996 MEDPAR data gave a figure of 183,310 discharges with a total Medicare reimbursement of $892 million. In both data sets, dermatology-specific DRGs show a decrease over time, although dermatology-related DRGs generally showed an opposite increasing pattern. The top 10 states reimbursed by Medicare in 1996 for the discharges grouped under the DRGs mentioned above were New York, California, Pennsylvania, Florida, Texas, Ohio, Illinois, Michigan, New Jersey, and Massachusetts. CONCLUSION: Many patients are admitted annually for skin disease. The minority are admitted by dermatologists.

South Florida survey on the relationship between academic medical centers and community physicians.

BACKGROUND: Little is known about the relationship between academic medical centers (AMCs) and community physicians (CPs). We examined this relationship for an individual specialty-dermatology. METHODS: South Florida dermatologists were queried regarding their practice and referral patterns, as well as the effect of managed care on these patterns. RESULTS: On average, the respondents see 7,342 patients annually. Ninety-eight percent refer one or more patients for aid in therapy (39%) and diagnosis (27%). Most were satisfied with the amount (63%) and quality (77%) of the service provided. Overall, only 0.2% of patients are referred. Sixty percent reported that managed care caused alterations in referral patterns. CONCLUSIONS: We found that, although community dermatologists diagnose and treat the vast majority of patients with skin disease seen by dermatologists, they also use and are satisfied with the AMC's services. Changes in referral patterns have occurred but have not negatively affected the relationship between the AMC and the CP.