A comparison of vascular inflammation in psoriasis, rheumatoid arthritis, and healthy subjects by FDG-PET/CT: a pilot study.

OBJECTIVE: Psoriasis (PSO) and rheumatoid arthritis (RA) increase cardiovascular diseases (CVD) beyond traditional risk factors. Vascular inflammation has previously been demonstrated to be present in PSO and RA using [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging. However, vascular inflammation has not been compared in these two disorders relative to a healthy reference population. Thus, vascular inflammation was quantitatively assessed in patients with PSO (n=10), RA (n=5), and healthy subjects (n=10) using FDG-PET/CT. METHODS: FDG-PET/CT mean standardized uptake value (SUVmean) was determined slice by slice within the ascending, aortic arch, descending thoracic, suprarenal abdominal, and infrarenal abdominal aorta, and the mean metabolic volumetric product (MVPmean) was then calculated for each aortic subsegment. Plasma lipids and metabolic and inflammatory markers were also assessed. RESULTS: CVD risk profiles were largely similar across groups. After adjustment for CV risk factors, regional aortic vascular inflammation based on MVPmean was elevated for both PSO (beta coefficients 0.31-1.47, p<0.001) and RA (beta coefficients 0.15-0.69, p<0.05) compared to healthy subjects. CONCLUSIONS: These observations using FDG-PET/CT to estimate vascular inflammation support epidemiological findings of premature atherosclerosis in PSO and RA. The use of FDG-PET/CT to investigate vascular inflammation across systemic inflammatory diseases warrants further examination in larger study populations.

Sarcoidosis and psoriasis: a case series and review of the literature exploring co-incidence vs coincidence.

IMPORTANCE: Sarcoidosis is a chronic multisystem disorder characterized by the formation of noncaseating epithelioid cell granulomas affecting multiple organ systems. The role of the type 1 helper T (T(H)1) cell in sarcoidal granuloma formation has been well documented, and the T(H)17 pathway in sarcoidosis is just now being investigated. T(H)17 cells are also known to involved in the pathogenesis of psoriasis, and the coexistence of sarcoidosis and psoriasis is mechanistically plausible based on potential shared underlying immunologic pathways. OBSERVATIONS: We report a case series of 7 patients with sarcoidosis and psoriasis vulgaris. All patients had psoriasis ranging from limited disease to involvement of 30% of their body surface area and had evidence of pulmonary sarcoidosis. Three of these patients also had cutaneous sarcoidosis, and 1 of these patients had evidence of both psoriasis and sarcoidosis in the same cutaneous specimen. CONCLUSIONS AND RELEVANCE: We report a case series of concomitant sarcoidosis and psoriasis, suggesting that common pathogenesis involving the T(H)1 and T(H)17 pathways may be responsible for this disease association. Although additional data are needed to clarify this association, this observation may lead to important understanding of the pathophysiologic and therapeutic management in these disorders.

Abnormal lipoprotein particles and cholesterol efflux capacity in patients with psoriasis.

OBJECTIVES: Psoriasis is a Th-1/17 mediated inflammatory disease associated with increased risk of cardiovascular disease (CVD). Inflammation may modulate lipoprotein particle number and directly impair HDL functions, in particular reverse cholesterol transport (RCT). We sought to study how chronic in vivo inflammation modulates lipoprotein particle composition using nuclear magnetic resonance spectroscopy (NMR) and HDL efflux in psoriasis. METHODS AND RESULTS: We prospectively enrolled a consecutive sample of patients with psoriasis (n = 122) and compared lipoprotein and metabolic risk factors to patients without psoriasis (n = 134). Fasting lipids, insulin, glucose were measured by standard assays, and lipoprotein concentration and size were measured by NMR. In a random subset (n = 100 each group), HDL efflux capacity was quantified using a validated ex vivo system involving the incubation of macrophages with apolipoprotein B-depleted serum from patients. Traditional lipid concentrations were similar in both groups except for HDL concentration which was lower in psoriasis (43 mg/dl (36-58) vs 50 (42-62), p < 0.01). However, NMR showed an atherogenic profile in psoriasis similar to that observed in diabetes, with significant increase in LDL particle concentration [1210.5 (1002-1498) vs 1115 (935-1291), p = 0.02] with decrease in LDL size [20.6 (20.3-21.1) vs 21.3 (20.6-21.1), p < 0.001] beyond CV risk factors and HOMA-IR (p = 0.001). Finally, HDL efflux capacity was lower in psoriasis compared to controls in fully adjusted models (beta -0.14, p = 0.001). CONCLUSIONS: These data support a more atherogenic lipoprotein profile by NMR and decreased HDL efflux capacity in psoriasis patients compared to controls beyond CVD risk factors. The abnormal lipoprotein particle composition and HDL efflux capacity in psoriasis may provide a link between psoriasis and CVD.

Oral curcumin in the treatment of moderate to severe psoriasis vulgaris: A prospective clinical trial.

BACKGROUND: There is a need for safe, inexpensive, and effective psoriasis therapies. Many anecdotal accounts of patients' successful treatment with the alternative medicine curcumin exist. OBJECTIVE: We sought to determine the safety and efficacy of oral curcumin in patients with psoriasis. METHODS: We conducted a phase II, open-label, Simon's two-stage trial of 4.5 g/d of oral curcuminoid C3 complex in patients with plaque psoriasis. End points included improvement in Physicians Global Assessment score, Psoriasis Area and Severity Index score, and safety end points throughout the study. RESULTS: The intention-to-treat analysis response rate was 16.7% (95% confidence interval: 2%, 48%) and both responders achieved a Psoriasis Area and Severity Index 75 score. There were no study-related adverse events that necessitated participant withdrawal. LIMITATIONS: Small sample size and lack of placebo group are limitations. CONCLUSION: The response rate was low and possibly caused by a placebo effect or the natural history of psoriasis. Large placebo-controlled studies are necessary before recommending oral curcumin as a psoriasis treatment.

Srcasm overexpression in psoriasis-insights into pathogenesis.

BACKGROUND: Psoriasis is a prevalent, chronic cutaneous disorder associated with a T-cell lymphocytic infiltrate and altered keratinocyte growth. Some of the molecular features of enhanced keratinocyte growth include increased growth factor receptor activation leading to enhanced cellular tyrosine kinase activity. Receptor tyrosine kinases, including the epidermal growth factor (EGF) receptor, are important regulators of keratinocyte growth, and increased activity of this receptor has been detected in psoriasis. A recently discovered, novel regulator of Src tyrosine kinases, termed Src-activating and signaling molecule (Srcasm), has been shown to modulate EGF signaling and promote differentiation in human keratinocytes. Given the properties of Srcasm, it would be of interest to characterize its expression in psoriasis. In this study, the levels of Srcasm mRNA and protein are characterized, and the relationship of these experimental observations to the psoriasis pathogenesis is discussed. METHODS: The levels of Srcasm mRNA were determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) on RNA isolated from unremarkable and lesional patient tissue. These data were supplemented by performing radioactive in situ hybridization on formalin-fixed biopsy specimens of psoriatic lesions and unremarkable epidermis. Expression of Srcasm protein was evaluated by protein immunohistochemistry and Western blotting of protein lysates derived from patient samples. RESULTS: All experimental modalities show that levels of Srcasm mRNA and protein were elevated in psoriatic lesions compared to unremarkable epidermis. CONCLUSIONS: Increased levels of Srcasm mRNA and protein are seen in psoriasis. Given what is known regarding Srcasm function, increased levels of this molecule in keratinocytes may represent a cell compensatory mechanism that is primed to re-establish a physiologic differentiation program.

Gene expression profiling of porokeratosis demonstrates similarities with psoriasis.

BACKGROUND: Porokeratosis (PK) is a clinically heterogeneous entity associated with sharply demarcated, annular, or serpiginous lesions with a hyperkeratotic ridge. This disorder is associated with aberrant keratinocyte differentiation that histologically manifests as a stack of parakeratin termed the cornoid lamella; this structure represents the peripheral hyperkeratotic ridge of clinical lesions. Histologically, the keratinocytes forming the cornoid lamella demonstrate an altered differentiation program. However, the molecular basis of PK remains incompletely understood. METHODS: As a first step in characterizing PK at the molecular level, gene expression profiling was performed on a cornoid lamella isolated from a large, Mibelli-type porokeratotic lesion. As a control, gene expression profiling of peripheral uninvolved epidermis was also performed. The gene expression profile of cornoid lamellar keratinocytes was compared with similar profiles obtained from a psoriatic plaque and cutaneous squamous cell carcinoma. RESULTS: Our study demonstrates a striking similarity between the gene expression profiles of PK and psoriasis. In addition, novel markers of the porokeratotic keratinocytes were identified, including keratin 16, S-100 A8 and A9, and connexin 26. CONCLUSIONS: This study supports the hypothesis that PK is a disorder of hyperproliferative keratinocytes exhibiting similarity at the molecular level to psoriasis. Consequently, some therapeutic modalities efficacious for psoriasis may be of benefit in PK.

Photo recall effect in association with cefazolin.

Patients in remission from local dermatitis secondary to external beam radiation treatments occasionally experience recurrence with systemic chemotherapy, a reaction termed radiation recall. Chemotherapy-induced photo recall from a prior exposure to the sun also has been reported. Rare reports describe photo recall effects from more commonly used medications. We report the case of a patient who developed a photo recall reaction after treatment with cefazolin. Results of the shave biopsy were consistent with a mild phototoxic eruption.