Immunogenicity, efficacy, and safety of CoronaVac and Pfizer/BioNTech mRNA vaccines in patients with psoriasis receiving systemic therapies: A prospective cohort study.

BACKGROUND AND OBJECTIVES: Evidence of immune response to COVID-19 vaccine in psoriasis patients on biological agents is lacking. This study aimed to evaluate SARS-CoV-2 antibody levels following vaccination with CoronaVac or Pfizer/BioNTech mRNA in patients using biological agents or methotrexate, high-titer antibody levels achievement rate, and impact of medications on immunogenicity. METHODS: This noninterventional, prospective cohort study included 89 patients and 40 controls vaccinated with two doses of inactivated (CoronaVac) or Pfizer/BioNTech mRNA vaccines. Anti-spike and neutralising antibodies were analysed before and three to six weeks after the second dose. Adverse effects and symptomatic COVID-19 were assessed. RESULTS: Median anti-spike and neutralising antibody titers after CoronaVac were significantly lower in patients than controls (57.92 U/mL vs 125.4 U/mL, and 1/6 vs 1/32, respectively, p < 0.05). Patients were less likely to achieve high-titer anti-spike antibody levels (25.6 % vs 50 %). Infliximab was associated with attenuated vaccine response. Pfizer/BioNTech vaccine induced comparable median anti-spike (2,080 U/mL vs 2,976.5 U/mL,) and neutralising antibody levels (1/96 vs 1/160) in patients and controls, respectively (p > 0.05). High-titer anti-spike and neutralising antibodies development rates were comparable among patients and controls (95.2 % vs 100 %, and 30.4 % vs 50.0 %, respectively, p > 0.05). Nine (10.1 %) COVID-19 cases- all mild - were identified. Psoriasis flare was seen in 6.74 %, mostly after Pfizer/BioNTech vaccine. CONCLUSION: Psoriasis patients treated with biological agents and methotrexate developed similar response to mRNA vaccine but weaker response to inactivated vaccine. Infliximab reduced response to the inactivated vaccine. Adverse effects were more frequent with mRNA vaccine, but none was severe.

Biologic Therapy Carries a Very Low Risk of Reactivation in Hepatitis B Surface Antigen-Negative Phase of Hepatitis B.

BACKGROUND: The risk of hepatitis B reactivation in hepatitis B surface antigen-negative phase of hepatitis B virus-infected patients exposed to biologic agents is not clear. We aimed to investigate the reactivation rate in hepatitis B surface antigen-negative phase of hepatitis B virus-infected patients after biologic therapy. METHODS: Patients followed at gastroenterology, rheumatology, and dermatology clinics with a diagnosis of immune-mediated inflam matory diseases were screened. Immune-mediated inflammatory diseases patients exposed to biologic agents with a negative hepatitis B surface antigen and positive hepatitis B core immunoglobulin G antibody were included in the study. RESULTS: We screened 8266 immune-mediated inflammatory disease patients, and 2484 patients were identified as exposed to biologic agents. Two hundred twenty-one patients were included in the study. The mean age was 54.08 ± 11.69 years, and 115 (52.0%) patients were female. The median number of different biologic subtype use was 1 (range: 1-6). The mean biologic agent exposure time was 55 (range: 2-179) months. One hundred and fifty-two (68.8%) patients used a concomitant immunomodulatory agent, and 84 (38.0%) patients were exposed to corticosteroids during biologic use. No hepatitis B reactivation with a reverse seroconversion of hepatitis B surface antigen positivity was seen. Antiviral prophylaxis for hepatitis B was applied to 48 (21.7%) patients. Hepatitis B virus-DNA was screened in 56 (25.3%) patients prior to the biologic exposure. Two patients without antiviral prophylaxis had hepatitis B virus-DNA reactivation with a negative hepatitis B surface antigen during exposure to the biologic agent. CONCLUSION: We found 2 reactivations and no hepatitis B surface antigen seroconversion in our cohort. Antiviral prophylaxis for patients exposed to biologic agents may need to be discussed in more detail.

Psoriasis and the liver: problems, causes and course.

BACKGROUND/OBJECTIVES: Psoriasis patients have a higher risk of liver abnormalities such as non-alcoholic fatty liver disease (NAFLD), drug-induced hepatitis, alcoholic hepatitis and neutrophilic cholangitis, than the general population. Associated liver disease limits therapeutic options and necessitates careful monitoring. The aim of the study was to identify liver problems in psoriasis patients and to investigate the underlying causes as well as their course. METHODS: The files of 518 psoriasis patients were retrospectively reviewed. Among these, 393 patients with relevant laboratory data were analysed for liver enzymes and their relation to the known risk factors for liver disease (obesity, diabetes mellitus, alcohol consumption, hepatotoxic medications, dyslipidemia, psoriatic arthritis and infectious hepatitis). RESULTS: Among 393 patients, 24% and 0.8% developed liver enzyme abnormalities and cirrhosis, respectively. The most common factors associated with pathological liver enzymes were drugs (57%) and NAFLD (22%). Other rare causes were alcoholic hepatitis, viral hepatitis, neutrophilic cholangitis, autoimmune hepatitis and toxic hepatitis due to herbal therapy. Drug-induced liver enzyme abnormalities were reversible whereas in patients with NAFLD transaminases tended to fluctuate. One patient with herbal medicine-related cirrhosis died of sepsis. CONCLUSION: Liver enzyme abnormalities are common in psoriasis patients and are mostly associated with drugs and NAFLD. Although most cases can be managed by avoiding hepatotoxic medications and close follow up, severe consequences like cirrhosis may develop.

Atypical presentations of eosinophilic fasciitis.

Eosinophilic fasciitis is an uncommon connective tissue disease that may mimic and overlap with other sclerosing disorders such as morphea and lichen sclerosus. Herein, we report four patients (two men and two women, aged 16-64 yeas) with eosinophilic fasciitis. There was overlap with both morphea and lichen sclerosus in 2 patients and with morphoea alone in 1 patient. Magnetic resonance imaging (MRI) was used for diagnosis in three patients and for assessing treatment response in one patient. Eosinophilic fasciitis may co-exist with morhoea and lichen sclerosus. In view of the overlapping clinical and histopathological features of these disorders, MRI may be helful in delineating the conditions by detecting involvement of fascia.

Interstitial Mycosis Fungoides With Lichen Sclerosus-Like Clinical and Histopathological Features.

Mycosis fungoides (MF) simulates a variety of dermatologic disorders histopathologically and clinically, well deserving the designation of a great mimicker. Interstitial MF is a rare, but well-recognized histopathological variant resembling the interstitial form of granuloma annulare or the inflammatory phase of morphea. From a clinical standpoint, MF can have a wide array of manifestations, including an anecdotal presentation with lesions clinically suggestive of lichen sclerosus (LS). We herein report a 25-year-old man with a history of patch-stage MF who later developed widespread LS-like lesions histopathologically consistent with interstitial MF. In some biopsies, additional features resembling LS were discerned. We think that our case might represent a unique variant of interstitial MF presenting with LS-like lesions. The diagnostic challenge arising from this uncommon presentation is discussed together with review of the literature.

Erlotinib induced ectropion following papulopustular rash.

BACKGROUND: Erlotinib is a targeted anti-cancer drug which acts through the inhibition of epidermal growth factor receptor (EGFR). MAIN OBSERVATIONS: A 79-year-old developed bilateral ectropion after he received erlotinib treatment for lung adenocarcinoma. The ectropion completely resolved with symptomatic treatment without any modification in erlotinib therapy. CONCLUSIONS: EGFR inhibitors are frequently associated with a variety of mucocutaneous adverse events. Ocular toxicity associated with these agents has been reported rarely. We present this case to underline the importance of recognition of newly reported cutaneous and ocular adverse events of targeted therapies.

Growth arrest-specific 6 and cardiometabolic risk factors in patients with psoriasis.

OBJECTIVES: An increased risk for cardiovascular disease with psoriasis has been reported. Growth Arrest-Specific 6 (GAS6) amplifies pro-inflammatory endothelial cell activation via TAM receptors. However, it also inhibits inflammation by multiple mechanisms including phagocytosis. The objective of this study was to investigate whether plasma GAS6 levels are associated with conventional cardiometabolic (CM) risk factors in patients with psoriasis. METHODS: Forty patients diagnosed with psoriasis (22 male, mean age: 43.3 ± 13.8 years) and 40 age-/sex-matched healthy controls (22 male, mean age: 39.3 ± 8.9 years) were included in the study. CM risk factors (hypertension, hyperlipidemia, diabetes mellitus, and cigarette smoking) were identified. GAS6 levels were measured by ELISA. RESULTS: There were no significant differences between the plasma GAS6 levels of patients with psoriasis compared to the control group (6.6 ± 2.0 ng/mL, 7.6 ± 2.8 ng/mL, respectively, P > 0.05). However, GAS6 levels of patients with psoriasis having a smoking history (n = 11) were significantly lower than both patients with psoriasis who had no smoking history (n = 29) and controls (5.5 ± 1.7 ng/mL, 6.9 ± 1.9 ng/mL, 7.6 ± 2.8 ng/mL, respectively, P < 0.05). Similarly, psoriasis patients with at least one CM risk factor showed lower GAS6 levels compared to subjects without any CM risk factor (5.7 ± 1.7 ng/mL, 7.3 ± 2.0 ng/mL, P < 0.01). There was no correlation between the GAS6 level, disease duration or PASI score (r = 0.150, -0.150, and P = 0.310, 0.398, respectively). CONCLUSIONS: This pilot study provides the first evidence in humans for an association between low plasma GAS6 levels and conventional risk factors in psoriasis. Further large scale, prospective studies are needed to confirm these results.

The risk of tuberculosis in patients with psoriasis treated with anti-tumor necrosis factor agents.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) antagonist treatment is associated with 1.6 to 27 times higher risk of tuberculosis (TB). OBJECTIVE: To find TB incidence of psoriasis patients treated with TNF- α antagonists and define risk factors related with this condition in a country with moderately high risk of TB. METHODS: Three hundred seventy psoriasis patients treated by anti-TNF agents in four referral centers were included. The data on the characteristics of the patients, TB history, tuberculosis skin test results, anti-TNF agent type and exposure time, localization of TB, and isoniazide prophylaxis state were analyzed. RESULTS: Four patients (1.08%) developed TB, three pulmonary and one gastrointestinal, 2-23 months after initiating anti-TNF agents. Other than the patient with gastrointestinal TB, who was using methotrexate and corticosteroid concomitantly, none had contributing risk factors for TB. Two patients developed pulmonary TB in spite of chemoprophylaxis. Three patients with pulmonary TB completely recovered following antiTB treatment whereas patients with gastroinrestinal TB developed renal failure. LIMITATIONS: The major limitation of the study is the lack of a diseased control group, which enables us to compare the risk of psoriatics with that of patients having other inflammatory diseases. CONCLUSION: Tuberculosis is a rare but a severe complication of anti-TNF treatment and may develop in spite of chemoprophylaxis. The risk of TB in psoriasis patients in the present study is comparable to literature mostly based on rheumatology patients.

Assessment of arterial stiffness and cardiovascular hemodynamics by oscillometric method in psoriasis patients with normal cardiac functions.

Arterial stiffness is associated with increased cardiovascular risk. Pulse wave velocity (PWV) and augmentation index (AIx) are non-invasive markers for assessment of arterial stiffness. Increased arterial stiffness is associated with atherosclerosis in patients with psoriasis. Previous studies have shown that high neutrophil-to-lymphocyte ratio (NLR) predicts poor cardiovascular outcome. The aim of this study was to evaluate arterial stiffness and cardiovascular hemodynamics by oscillometric method in psoriasis patients with normal cardiac functions. Fifty consecutive patients with the diagnosis of psoriasis and 50 controls were included in the study. NLR was calculated as the ratio of neutrophil count to lymphocyte count. All patients underwent echocardiographic examination. Measurements of arterial stiffness were carried out using a Mobil-O-Graph arteriograph system. Fifty patients with psoriasis (26 male, mean age 43.3 ± 13.2 years) and 50 controls (33 male, mean age 45.0 ± 6.1 years) were included into the study. The distribution of cardiovascular risk factors was similar between the two groups, and NLR was significantly higher in patients with psoriasis (2.74 ± 1.78 versus 1.82 ± 0.52, p = 0.002). There was a weak correlation between NLR and PASI score without reaching statistical significance (r = 0.300, p = 0.060). While echocardiographic and hemodynamic parameters were comparable between psoriasis and control groups, heart rate was significantly higher in psoriasis group (81.5 ± 15.1 and 75.2 ± 11.8 beats/min, p = 0.021). Psoriasis patients had significantly higher AIx and PWV values as compared to controls (25.8 ± 13.1 versus 17.4 ± 12.3%, p = 0.001 and 6.78 ± 1.42 versus 6.18 ± 0.80 m/s, p = 0.011, respectively). AI and PWV were significantly associated with psoriasis when adjusted by heart rate (p = 0.005, odds ratio 1.04, 95% confidence interval 1.01-1.08 and p = 0.035, odds ratio 1.52, 95 % confidence interval 1.02-2.26, respectively). PWV significantly correlated with blood pressure, lipid levels, and several echocardiographic indices. AIx only correlated with left atrial diameter (r = 291, p = 0.040). Linear regression analysis was performed to find predictors of PWV. Central systolic blood pressure, left atrial diameter, and total cholesterol were independent predictors of PWV. PWV and AIx were significantly higher in patients with psoriasis. Assessment of arterial stiffness parameters may be useful for early detection of cardiovascular deterioration in psoriasis patients with normal cardiac functions. Novel inflammatory biomarkers such as NLR may elucidate the mechanism of vascular dysfunction in such patients.

Two Clinically Unusual Cases of Folliculotropic Mycosis Fungoides: One with and the Other without Syringotropism.

Mycosis fungoides is the most common form of cutaneous T-cell lymphoma, and it rarely exhibits predilection for hair follicle and eccrine gland infiltration. Here, we present 2 similar cases that display folliculotropism with varying amounts of follicular mucinosis, with and without syringotropism. The features observed in both cases were cystic, comedo-like, acneiform lesions; generalized involvement with loss of body hair; pruritus; and hidradenitis suppurativa-like lesions. Hypohidrosis as well as nail and palmoplantar involvement with lichen planopilaris-like clinical features were unique characteristics of the first case. Despite the well-known aggressive behavior of follicular mycosis fungoides, the presented cases had a subtle, slowly progressive, but persistent, clinical course. Folliculotropic and syringotropic mycosis fungoides are variants of cutaneous T-cell lymphoma. Clinical presentations might be challenging, and multiple, deep biopsy specimens containing adnexal structures are required for this critical diagnosis. Aggressive treatment may not be necessary in cases having an indolent course, especially in those with syringotropism.

Enhanced functional stability of plasminogen activator inhibitor-1 in patients with livedoid vasculopathy.

Livedoid vasculopathy (LV) is a chronic, recurrent, painful cutaneous disease with distinctive clinical features and an uncertain etiology. The skin lesions are recognizable by focal purpura, depigmentation and shallow ulcers. Thrombophilic conditions occur frequently in patients with LV. While no definitive treatment exists for LV, smoking cessation, antiplatelet therapy, immunosuppressive treatment, and anabolic steroids are often included in the therapeutic ladder. Recently, a possible link between LV and impaired fibrinolysis was established as cutaneous LV lesions responded to tissue plasminogen activator (t-PA) infusion suggesting that inhibition of the fibrinolysis through plasminogen activator inhibitor-1 (PAI-1) activity may determine the disease course in patients with LV. In this study, we investigated PAI-1 antigen (Ag) and activity levels in 20 patients with biopsy proven LV (mean age 26 ± 11, M/F = 7/13, median disease duration 3.5 years). All patients received antiplatelet treatment with aspirin and/or dipyrimadole and 14 patients received anabolic steroids or immunosuppressive treatment. Fasting PAI-1 Ag and activity levels were measured at 9 AM in all patients. Both Ag (34 (26) ng/ml) (median (interquartile range)) and specific activity (17 (23) IU/fmole) levels of PAI-1 were moderately elevated in LV patients compared to the controls, however, PAI-1 kinetic studies demonstrated markedly enhanced stability of PAI-1 activity in plasma from patients with LV. Specific activity at 16 h was significantly higher than expected specific activity levels (7 (11) vs. 0.07 (0.09) IU/fmole, P < 0.01). While the exact mechanism of increased stability of PAI-1 activity is not known, it may be due to post-translational modifications or increased binding affinity for a stabilizing cofactor. In conclusion, enhanced stability of PAI-1 may contribute to the pathophysiology of LV, and systemic or local treatment with PAI-1 inhibitors may offer a potential treatment alternative in patients with LV.

Topical 8-methoxypsoralen increases the efficacy of narrowband ultraviolet B in psoriasis.

BACKGROUND: A combination of oral psoralen with narrowband ultraviolet B (UVB), defined as 'psoralen-narrowband UVB', was shown to have a superior efficacy than UVB alone and even a comparable efficacy to psoralen and ultraviolet A in psoriasis. OBJECTIVE: To find out whether topical psoralen-narrowband UVB provides any additional benefit to narrowband UVB alone in psoriasis. METHODS: Nineteen patients with plaque psoriasis were included. Phototherapy was given three times per week. Two symmetrical lesions were selected as target lesions. In the first 12 sessions of phototherapy, the target lesion on one side was treated with 1% 8-methoxypsoralen (MOP) gel 30 min before UVB radiation whereas the target lesion on the other side served as a control. Target lesion scores were assessed at baseline, third, sixth, ninth and 12th sessions. Side effects were recorded. RESULTS: Sixteen patients completed the study. Target lesion scores decreased significantly on both sides (P<0.0001). The mean percentage of decreases was greater on the 8-MOP-applied sides compared with the control sides for all assessments, but the difference was statistically significant only at the ninth session (37.7% vs. 58.6%, P=0.043). Pigmentation was frequently seen in 8-MOP gel-applied lesions. CONCLUSION: Topical 8-MOP gel plus narrowband UVB has greater efficacy than narrowband UVB alone in psoriasis.

Repigmentation and curling of hair after acitretin therapy.

Drug-induced hair colour and texture changes have been reported rarely. We describe a 70-year-old woman with psoriasis who noticed darkening of her previously white hair, which also gained a curly appearance after 6 months of acitretin treatment. We present this case to emphasize that acitretin can be added to the list of drugs that induce changes in hair colour and texture.

Leukemic vasculitis: an unusual manifestation of leukemia cutis.

Leukemia cutis is frequently observed as papules, nodules, and plaques, but unusual clinical manifestations rarely occur. We report a 64-year-old woman with acute myeloid leukemia M1 who presented with erythematous papules and vesiculobullous lesions limited to the arms, hands, and neck in addition to purpuric papules on the legs. Because of the symmetric distal involvement and vesiculobullous nature of the skin lesions, the differential diagnosis included erythema multiforme and vasculitis. However, a skin biopsy specimen revealed infiltration with a striking predominance of blast cells in the dermis. These cells were also observed within the walls of the venules along with fibrin. Leukemia cutis associated with vasculitis was diagnosed. A few blast cells can be observed in many reactive dermatoses in patients with leukemia. However, in this patient a predominance of blast cells in the dermis and infiltration of vessel walls by these cells favored leukemic vasculitis.

Can topical calcipotriol be a treatment alternative in actinic keratoses? A preliminary report.

BACKGROUND: Recent research demonstrated that vitamin D, apart from calcium-related actions, has antiproliferative, prodifferentia-tive and immunomodulatory activities. OBJECTIVE: To determine whether actinic keratoses may benefit from the antiproliferative and prodifferentiative effects of topical vitamin D. MATERIALS AND METHODS: The study was an investigator-blinded, half-side comparison trial. Patients applied calcipotriol cream to one side and Ultrabase cream as placebo to the other side of the scalp and/or face for 12 weeks. The total number of actinic keratoses (AKs), diameters and total scores of the target lesions were determined at each visit. RESULTS: Nine patients were included, eight of whom completed the treatment. There was a statistically significant difference between the total number of AKs at baseline and at week 12 on calcipotriol applied side whereas no difference was detected on placebo applied side (p = 0.028 vs p = 1.00). The mean total score of the target lesions reduced significantly at week 12 on calcipotriol side; however, no significant reduction was found on placebo side (p = 0.017 vs p = 0.056). Although side effects were more common on calcipotriol side, the difference was not statistically significant. CONCLUSION: Topical calcipotriol may show promise in the treatment of actinic keratoses. More studies are needed to confirm its efficacy.