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Background
The heartbreak of psoriasis...is a true statement. It is a chronic, relapsing disease that affects as many as 2% of the population and involves all races. There is a familial tendency and preliminary work has focused on chromosome 17q and 1q21. It is also associated with HLA-CW6, B13, and B17. The classic clinical appearance is a well-circumscribed erythematous patch with a silvery white scale occurring in a person in their 2nd to 3rd decade. It characteristically involves the extensor surfaces of the extremities, the sacral region, scalp, and nails. New lesions occur at sites of trauma (Koebnerization). Infections may trigger a new onset (see guttate psoriasis). This may be related to production of superantigens by the streptococcus. Drugs may also precipitate or exacerbate the disease including lithium, quinidine, clonidine, iodine, indomethacin, some beta-blockers, terfenadine, NSAIDS, ACE inhibitors, interferon-alpha, interleukin-2, isotretinoin, and antimalarial agents. In about 5% of cases, a seronegative polyarthritis occurs. In addition to these variants, pustular psoriasis is usually separated as a distinct entity.
OUTLINE
DISEASE ASSOCIATIONS CHARACTERIZATION ACTINIC KERATOSIS Are patients with psoriasis susceptible to the classic risk factors for actinic keratoses?
Paltiel O, Adler B, Herschko K, Tsukrov B, David M.
School of Public Health and the Department of Hematology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Arch Dermatol. 2004 Jul;140(7):805-10. Abstract quote
BACKGROUND: An increased prevalence of benign solar damage (eg, facial wrinkles) but not neoplastic lesions was observed among patients with psoriasis who were exposed to Dead Sea climatotherapy compared with controls.Objectives To compare the prevalence of actinic keratosis in psoriatic patients and controls and to assess whether known risk factors behave similarly in both groups.
DESIGN: Multicenter cross-sectional study.
SETTING: Dermatology clinics in 4 participating Israeli hospitals and at a Dead Sea clinic.
PARTICIPANTS: Adult subjects (n = 460) with plaque-type psoriasis were recruited from the Israel Psoriasis Association (volunteer sample) and from dermatology clinics (convenience sample). The control group (n = 738) consisted of nonimmunosuppressed patients attending these clinics for benign conditions unrelated to sun exposure, such as atopic or contact dermatitis.
MAIN OUTCOME MEASURES: Prevalence and distribution of actinic keratoses and odds ratios associated with skin, hair, and eye color and propensity or history of sunburn adjusted for age, ethnicity, and sun exposure.
RESULTS: Actinic keratoses were observed in 200 controls (27%) and 51 subjects (11%) (P<.001). This increased prevalence occurred in both sexes, participants aged 35 years or older, all ethnic groups, smokers, and nonsmokers. The anatomical distribution of lesions did not substantially differ between subjects and controls. In multivariate analysis, psoriasis conferred a protective effect (odds ratio, <1), as did dark skin, dark eyes, and a history of severe sunburn in childhood. However, significant interactions were observed between psoriasis and hair color as well as psoriasis and propensity to sunburn, whereby a linear association was observed for controls but not for patients with psoriasis.
CONCLUSIONS: Psoriasis confers protection against actinic keratosis. Hair color and propensity to sunburn exert differential effects among psoriatic patients and controls.CROHN'S DISEASE
Connections between psoriasis and Crohn's disease.Najarian DJ, Gottlieb AB.
University of Virginia School of Medicine, and the Clinical Research Center, University of Medicine and Dentistry of New Jersey-The Robert Wood Johnson Medical School.
J Am Acad Dermatol. 2003 Jun;48(6):805-21. Abstract quote The prevalence of psoriasis in patients with Crohn's disease (CD) is higher than chance would allow if they were mutually exclusive diseases. A close examination reveals genetic and pathologic connections between these diseases. An appreciation for the role of tumor necrosis factor-alpha in both diseases has proven very important.
Increased levels of this inflammatory cytokine have been measured in CD lesions, and in 1997 a clinical trial demonstrated the response of this disease to infliximab, a monoclonal antibody specific for tumor necrosis factor-alpha. A subsequent clinical trial evaluated infliximab in a patient with CD and psoriasis, another disease in which increased levels of tumor necrosis factor-alpha are seen in lesions.
Scientists noticed the marked skin improvement of this patient and later demonstrated the efficacy of infliximab for psoriasis in a randomized, double-blind, placebo-controlled trial. Thus, an appreciation for connections between psoriasis and CD can suggest novel therapeutic strategies with ensuing benefits to patients.
This article reviews epidemiologic, genetic, and pathologic connections between psoriasis and CD and discusses pharmaceuticals targeting inflammatory mediators common to each disease. (J Am Acad Dermatol 2003;48:805-21.) Learning objective: At the completion of this learning activity, participants should understand how psoriasis and Crohn's disease are related at epidemiologic, genetic, and pathological levels and should appreciate how to use this knowledge to treat these diseases.HUMAN PAPILLOMAVIRUS
Increased Prevalence of Human Papillomavirus in Hairs Plucked From Patients With Psoriasis Treated With Psoralen-UV-A.
Wolf P, Seidl H, Back B, Binder B, Hofler G, Quehenberger F, Hoffmann C, Kerl H, Stark S, Pfister HJ, Fuchs PG.
Department of Photodermatology, Department of Dermatology, Institute of Pathology, and Institute of Medical Informatics, Statistics, and Documentation, Karl-Franzens-University, Graz, Austria.
Arch Dermatol. 2004 Mar;140(3):317-24 Abstract quote.
BACKGROUND: Patients with psoriasis treated with psoralen-UV-A (PUVA) are at increased risk of skin cancer; however, the exact causes of this increased incidence are not well understood. It has been suggested that PUVA may increase expression of the tumorigenic agent human papillomavirus (HPV) in skin by directly stimulating virus replication, immune suppression, or both, thereby leading to skin cancer formation.
OBJECTIVE: To determine whether HPV DNA prevalence in the skin is increased after long-term PUVA treatment.
DESIGN: Screening for the presence of HPV sequences in DNA isolated from plucked body hairs of patients with psoriasis with a history of PUVA exposure and a history of skin cancer (group A), PUVA exposure and no history of skin cancer (group B), and no PUVA exposure and no history of skin cancer (group C).
SETTING: University hospital.Patients and METHODS: Hair samples were obtained from 81 patients with psoriasis (56 men and 25 women; mean age, 52 years), including 16 in group A (mean number of PUVA exposures, 702), 35 in group B (mean number of PUVA exposures, 282), and 30 in group C. DNA was isolated from the hair samples and analyzed by polymerase chain reaction with the use of 2 nested primer systems specific for epidermodysplasia verruciformis-associated or related and genital or mucosal virus types, respectively.
RESULTS: The rate of HPV DNA positivity was significantly higher in groups A (73% [11/15]) and B (69% [24/35]) than in group C (36% [10/28]) (A + B vs C, P =.009; chi(2) test; age adjusted).Conclusion The prevalence of HPV in the skin (hair follicles) is increased in patients with psoriasis who have a history of PUVA exposure.LYMPHOMA
Lymphoma rates are low but increased in patients with psoriasis: results from a population-based cohort study in the United Kingdom.
Gelfand JM, Berlin J, Van Voorhees A, Margolis DJ.
Department of Dermatology and the Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadephia 19104, USA.
Arch Dermatol. 2003 Nov;139(11):1425-9 Abstract quote.
OBJECTIVE: To determine if the rate of lymphoma in patients with a history of psoriasis is different from the rate of lymphoma in patients without psoriasis.
DESIGN: Cohort study.
SETTING: Outpatient practices of general practitioners in the United Kingdom who contribute to the General Practice Research Database.
PATIENTS: The population studied was a sample of 10% of the patients 65 years or older registered with a general practitioner contributing to the General Practice Research Database between 1988 and 1996.
MAIN OUTCOME MEASURE: The rate of lymphoma in patients with psoriasis compared with the rate of lymphoma in patients without psoriasis.
RESULTS: There were 2718 patients who had psoriasis and 105 203 patients (the reference population) who did not have psoriasis. The median follow-up time was 46 months. We noted 276 lymphomas. Patients with psoriasis had a 2.95 relative rate of developing lymphoma (95% confidence interval, 1.83-4.76) compared with those without psoriasis. This estimate did not change after controlling for age and sex using the Cox multivariable proportional hazards model. The rate of lymphoma changed little when the patients treated with methotrexate or those who developed mycosis fungoides were excluded. Compared with the reference population, we found an additional 122 lymphomas per 100 000 patients annually among patients with psoriasis who were 65 years or older.
CONCLUSIONS: These results indicate that patients with psoriasis are at increased risk for developing lymphoma. Additional studies are necessary to determine if the increased rate of lymphoma is related to psoriasis severity, psoriasis treatment, or an interaction between these risk factors.MALIGNANCIES
Cancer risk in a population-based cohort of patients hospitalized for psoriasis in Sweden.Boffetta P, Gridley G, Lindelof B.
Unit of Environmental Cancer Epidemiology, International Agency for Research on Cancer, Lyon, France.
J Invest Dermatol 2001 Dec;117(6):1531-7 Abstract quote Studies of clinical series of psoriasis patients have suggested an increased risk of nonmelanoma skin cancer and melanoma; the risk of other neoplasms has rarely been studied. In order to assess the incidence of cancer in a nationwide series of psoriasis patients from Sweden, we followed up, for the years 1965-89, 9773 patients with a hospital discharge diagnosis of psoriasis made during 1965-83, who were alive and free from malignancy 1 y after first discharge.
We compared their incidence of neoplasms with that of the national population by computing standardized incidence ratios (SIR). We observed a total of 789 neoplasms [SIR 1.37, 95% confidence interval (CI) 1.28, 1.47]. There was an increase in the risk of cancers of the oral cavity and pharynx (SIR 2.80, 95% CI 1.96, 3.87), liver (SIR 1.91, 95% CI 1.28, 2.74), pancreas (SIR 1.56, 95% CI 1.02, 2.23), lung (SIR 2.13, 95% CI 1.71, 2.61), skin (squamous cell carcinoma, SIR 2.46, 95% CI 1.82, 3.27), female breast (SIR 1.27, 95% CI 1.00, 1.58), vulva (SIR 3.24, 95% CI 1.18, 7.06), penis (SIR 4.66, 95% CI 1.50, 10.9), bladder (SIR 1.43, 95% CI 1.03, 1.92), and kidney (SIR 1.56, 95% CI 1.04, 2.25). The risk of malignant melanoma was decreased (SIR 0.32, 95% CI 0.10, 0.74).
Despite some limitations (possible diagnostic misclassification, lack of data on treatment, relatively short follow-up), our study provides evidence against an increased risk of melanoma among patients hospitalized for psoriasis. In addition to nonmelanoma skin and genital cancers, patients hospitalized for psoriasis were at increased risk of several malignancies, in particular those associated with alcohol drinking and tobacco smoking.
PARANEOPLASTIC Spontaneous disappearance of psoriasis as presenting feature of oat-cell carcinoma of lung.
Lennard TW, Lennard AL.
Br Med J 1980 Nov 29;281(6253):1460-1 Psoriasis in association with prolactinoma: three cases.
Sanchez Regana M, Umbert Millet P.
Department of Dermatology, Hospital Sagrado Corazon, University of Barcelona, C/Paris 83-87 5th floor, 08029 Barcelona, Spain.
Br J Dermatol 2000 Oct;143(4):864-7 Abstract quote
We report three women with plaque-type psoriasis in whom increase in severity and extent of the skin lesions correlated with the development of a prolactinoma.
In all three patients, administration of bromocriptine, a dopamine agonist that suppresses the secretion of prolactin, improved the therapeutic response of the psoriasis.
To our knowledge, there are no reports of an association between psoriasis and prolactinoma. In recent years it has become apparent that prolactin plays an important part in the immune reactions and exerts a proliferative effect on human keratinocytes. We, therefore, discuss the part that prolactin may play in the pathogenesis of psoriasis.
DRUG ERUPTION Transient eruptive seborrheic keratoses associated with erythrodermic psoriasis and erythrodermic drug eruption: Report of two cases
Scott L. Flugman, MD
Steve A. McClain, MD
Richard A. F. Clark, MDStony Brook, New York
J Am Acad Dermatol 2001;45:S212-4 Abstract quote
The appearance of multiple seborrheic keratoses in association with underlying internal malignancy (known as the sign of Leser-Trelat) has generated much discussion and debate in the literature. However, comparatively few case reports exist that examine the appearance of multiple seborrheic keratoses associated with exfoliative erythroderma without underlying malignancy.
We report 2 cases in which multiple, biopsy-proven seborrheic keratoses appeared in conjunction with erythrodermic skin eruptions. The underlying diseases in these 2 patients included psoriasis and an eczematous drug eruption; in both cases the erythroderma resolved with appropriate treatment. After resolution of the erythroderma, the newly developed seborrheic keratoses proceeded to involute and gradually fall off. Neither of the patients exhibited any evidence of internal malignancy.
These cases represent the first reports of psoriasis and drug eruption as causes of erythroderma-induced transient eruptive seborrheic keratoses. Clinical and pathologic findings are consistent with previous descriptions of this entity.
PATHOGENESIS CHARACTERIZATION APOPTOSIS
Department of Pathology, Faculty of Medicine, Menofiya University, Shebein Elkom, Egypt.
BACKGROUND: Suppression of apoptosis is generally one of the accepted pathogenetic mechanisms for psoriasis and any epidermal hyperproliferative states. Survivin is a member of the inhibitor of apoptosis protein family mediating its apoptosis suppressive function by the inhibition of caspase pathway. Nuclear factor kappa B (NF-kappaB) is a transcription factor that regulates hundreds of genes including many critically involved in apoptosis. The aim of this study was to explore the role could be played by survivin and NF-kappaB in psoriasis and the link between them.
METHODS: Thirty cases of lesional psoriasis, 10 perilesional and 10 control specimens from normal skin were studied by immunohistochemical method for expression of survivin and NF-kappaB.
RESULTS: Survivin was detected in 73% of psoriatic lesions distributed either in epidermis, in endothelial cells of proliferating capillaries or in both of them. In non-psoriatic lesions either perilesional or control specimens, survivin was confined to basal layer of epidermis, significantly up regulated in psoriasis in comparison with non-psoriatic lesions (p = 0.0001). Nuclear expression of NF-kappaB was detected in 66% of psoriatic lesions; this active phosphorylated form was significantly over expressed in psoriasis in comparison with normal skin (p = 0.0004). Diffuse nuclear expression of NF-kappaB was significantly associated with up-regulation of survivin in psoriatic plaque (p = 0.03).
CONCLUSIONS: Survivin and NF-kappaB appeared to be important factors in the pathogenesis of psoriasis. Survivin could be the target of NF-kappaB mediating its death signal inhibition pathway in psoriasis.
School of Medicine, Celal Bayar University.
Background: Psoriasis is characterised by hyperproliferation and by aberrant differentiation. Blockage of the normal apoptotic process is one of the factors implicated in the pathogenesis.
Objective: To determine the apoptotic features by using TUNEL method and also bcl-2 and p53 expressions in psoriatic epidermis.
Materials and methods: Biopsies of 35 patients with psoriasis vulgaris and 14 normal skin were evaluated. Apoptotic cells were detected using the dUTP nick-end labelling assay; bc1-2 and p53 expressions were assessed by using immunohistochemical techniques. A semi-quantitative grading system (HSCORE) was used for comparison.
Results: Bcl-2 was strongly expressed in basal keratinocytes of normal skin, while no expression was observed in 13 (37.2%) of the psoriatic samples and it was weakly expressed in the spinous cell layer of 22 (62.8%) samples. Moderate p53 expression was observed in the psoriasis group, while it was weak in the control. The percentage of TUNEL positive cells were significantly increased in the psoriasis group (65+/-2.30) when compared with the control (32.84+/-7.16).
Conclusion: Apoptotic index besides bc1-2 and p53 expressions in psoriasis differ from normal epidermis. Down-regulation of bc1-2 is consistent with the dynamics of psoriasis but increased TUNEL positive cells and p53 expression has not been fully elucidated yet.CELL KINETICS
Background: Psoriasis vulgaris is a common chronic inflammatory dermatosis. Disorders in keratinocyte proliferation, differentiation, inflammation and immune dysregulation are the major factors implicated in the pathogenesis of psoriasis vulgaris.
Methods: The study was performed in skin specimens of 25 patients with psoriasis vulgaris and a control group of 10 individuals without a skin disease. Biopsy specimens from lesional and normal skin were analyzed by immunohistochemical method for expressions of Ki-67, Bcl-2, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL), tumor necrosis factor alpha (TNF-alpha) and nuclear factor kappa B (NF-kappaB). In addition, densities of mast cell infiltration were also investigated.
Results: Ki-67 and TUNEL indexes and TNF-alpha and NF-kappaB expressions were significantly higher in psoriatic epidermis than in normal epidermis (p < 0.05). There was no significant difference at Bcl-2 reactivity between the normal and the psoriatic epidermis (p > 0.05); however, Bcl-2 staining intensity of lymphocytes was higher in psoriatic lesions than in normal dermis (p < 0.05). Additionally, the number of mast cells was significantly higher in psoriatic dermis than in normal skin (p < 0.05).
Conclusions: There were several complex factors involved in the pathogenesis of psoriasis. We conclude that cellular damage and apoptosis temporarily coincide with epidermal proliferation during the course of psoriatic hyperplasia.CYTOKINES Arch Dermatol 1991;127:871 Interleukin-8
Transforming growth factor-alpha (TGF-alpha)Platelet activating factor, leukotriene B4 C5a anaphylatoxin ICAM-1 (CD54), ICAM-2, VCAM-1
Integrins
Selectins (E-selectin)IL-1, TNF-alpha, IFN-gamma, IL-4 IL-8 IL-8, TGF-alpha, phospholipase C/protein kinase C signal transduction system
Amphiregulin
Enhanced expression of heat shock proteinsVascular endothelial growth factor
Mediation of systemic vascular hyperpermeability in severe psoriasis by circulating vascular endothelial growth factor.Creamer D, Allen M, Jaggar R, Stevens R, Bicknell R, Barker J.
Department of Dermatology, King's College Hospital, Denmark Hill, London SE5 9RS, England.
Arch Dermatol 2002 Jun;138(6):791-6 Abstract quote BACKGROUND: Severe forms of psoriasis can be complicated by systemic microvascular hyperpermeability. Vascular endothelial growth factor (VEGF) possesses potent vascular permeability activity. We suggest that VEGF enters the systemic circulation and acts on microvessels to mediate hyperpermeability.
OBJECTIVES: To quantify renal microvascular permeability and circulating VEGF concentration in severe psoriasis, and to investigate the relationship between plasma VEGF concentration and skin and joint involvement.
DESIGN: Inception cohort studies of patients with generalized pustular psoriasis and plaque psoriasis.
SETTING: St John's Institute of Dermatology, London, England. PATIENTS: Twenty-two patients (15 men and 7 women) with moderate and severe psoriasis were recruited (age range, 29-77 years; mean age, 47 years); 5 had generalized pustular psoriasis, 2 had erythrodermic psoriasis, and 15 had moderate-severe plaque psoriasis. An age- and sex-matched control group of 17 individuals (10 men and 7 women) was recruited (age range, 29-69 years; mean age, 42 years).
RESULTS: There was pathological proteinuria in patients with relapsing generalized pustular psoriasis, (4-fold increase in urinary protein excretion rate in relapse compared with remission). In patients with moderate and severe psoriasis, mean plasma VEGF concentration during relapse was approximately 2.5 times greater than during remission (mean VEGF(relapse) = 257 pg/mL; mean VEGF(remission) = 103 pg/mL; P<.01). There was a correlation between extent of skin involvement and plasma VEGF level (mean VEGF(severe psoriasis) = 365 pg/mL; mean VEGF(moderate psoriasis) = 149 pg/mL; P =.03). There was a correlation between presence of psoriatic arthritis and plasma VEGF level (mean relapse VEGF(arthritis) = 277 pg/mL; mean relapse VEGF(nonarthritis) = 103.5 pg/mL; P =.03).
CONCLUSIONS: Generalized pustular psoriasis is accompanied by pathological proteinuria and elevated plasma VEGF levels. Plasma VEGF concentration is significantly elevated in patients with extensive skin and joint involvement and may act on renal microvasculature to induce hyperpermeability.
IMMUNE RECEPTORS
Innate immune-related receptors in normal and psoriatic skin.Curry JL, Qin JZ, Bonish B, Carrick R, Bacon P, Panella J, Robinson J, Nickoloff BJ.
Department of Pathology, Skin Cancer Research Laboratories, Loyola University Cancer Center, Maywood, Ill.
Arch Pathol Lab Med 2003 Feb;127(2):178-86 Abstract quote Context.-A precise role for the innate immune system in psoriasis remains to be determined. Surface receptors, including Toll-like receptors (TLRs) that recognize bacterial ligands and CD91, which recognizes heat shock proteins (HSPs), are implicated in both innate and adaptive immunity.
Objective.-Since skin is exposed to various exogenous stimuli, which can provoke or exacerbate psoriasis, we characterized expression and function of TLRs, CD91, and HSPs in normal and psoriatic skin.
Design.-A variety of skin-derived cells and blood-derived cells were analyzed both in vivo and in vitro; samples were obtained from 24 different individuals for innate immune-related receptor expression and function. By comparing and contrasting individuals with healthy skin and psoriatic patients, several specific differences were identified.
Results.-Immunohistochemistry-based expression profiling revealed TLR1 expression in epidermal dendritic cells (DCs) and dermal dendritic cells (DDCs) in normal skin, as well as in pre-psoriatic skin and psoriatic plaques, with enhanced basal layer keratinocyte (KC) expression in pre-psoriatic and psoriatic plaques compared with normal skin; TLR2 expression primarily by DDCs; and TLR4 expression by epidermal DCs and DDCs, with mid-epidermal-layer KCs displaying cell surface staining. No TLR9 or CD14 was detected on DCs or KCs, although psoriatic plaques contained CD14-positive macrophages. Analysis of psoriatic epidermis revealed HSPs 27, 60, and 70. Keratinocytes were CD91 negative, but CD91 was expressed by fibroblasts and DDCs in normal and pre-psoriatic skin, with prominent accumulation of CD91-positive DDCs in psoriatic plaques. Cultured KCs revealed no surface expression of TLR2, TLR4, TLR9, or CD91. Exposure of fibroblasts, but not KCs, to lipopolysaccharide or HSPs triggered nuclear factor (NF)-kappaB activation. Heat shock proteins did induce maturation of blood-derived DCs accompanied by increased interleukin-12 production and enhanced antigen-presenting function.
Conclusions.-These data demonstrate distinctive patterns of innate immune-related receptors by specific subsets of cells in normal and psoriatic skin, suggesting functional roles for HSPs and DCs in psoriasis.
MALESSEZIA FURFUR
Possible role of Malassezia furfur in psoriasis: modulation of TGF-beta1, integrin, and HSP70 expression in human keratinocytes and in the skin of psoriasis-affected patients.
Baroni A, Paoletti I, Ruocco E, Agozzino M, Tufano MA, Donnarumma G.
Department of Dermatology, and Department of Experimental Medicine: Microbiology and Clinical Microbiology, Second University of Naples, Naples, Italy.
J Cutan Pathol. 2004 Jan;31(1):35-42 Abstract quote.
BACKGROUND: Psoriasis is a disease characterized by an abnormal pattern of keratinocyte growth and differentiation. Malassezia furfur forms part of the normal human skin flora. It may also be involved in the pathogenesis of psoriasis. To define the role of M. furfur in the pathogenesis of psoriasis, we investigated how M. furfur regulates molecules involved in cell migration and proliferation. The experiments were performed using human keratinocytes and skin biopsies from M. furfur-positive and -negative psoriasis-affected patients. In addition, we examined the signal transduction mechanisms involved.
MATERIALS AND METHODS: Western blot analysis was performed on human keratinocytes lysates treated or untreated with M. furfur and on biopsies from healthy and psoriasis patients. Signal transduction mechanisms involved were evaluated by electrophoretic mobility shift assay using the AP-1 inhibitor curcumin.
RESULTS: We found that M. furfur up-regulates transforming growth factor-beta1 (TGF-beta1), integrin chain, and HSP70 expression in human keratinocytes via AP-1-dependent mechanism. In the biopsies of M. furfur-positive psoriasis-affected patients, an increase in TGF-beta1, integrin chains, and HSP70 expression was found.
CONCLUSION: Our data suggest that M. furfur can induce the overproduction of molecules involved in cell migration and hyperproliferation, thereby favoring the exacerbation of psoriasis.Srcasm
(Src-ACTIVATING AND SIGNALING MOLECULE)
Department of Dermatology, University of Pennsylvania Medical School, Philadelphia, PA, USA.
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.SUPERANTIGENS
J Am Acad Dermatol. 2005 Jul;53(1):67-72. Abstract quote
BACKGROUND: The aggravating role of Staphylococcus aureus superantigens is well known in atopic dermatitis (AD) but has not yet been proven in psoriasis (PS).
OBJECTIVE: We investigated the distribution of S aureus in the skin and nares of patients with AD, PS vulgaris, erythroderma, skin infections, and sepsis, and in healthy control subjects. A Staphylococcal enterotoxin test-reversed passive latex agglutination (SET-RPLAR) test was performed to determine Staphylococcal enterotoxins A, B, C, and D.
RESULTS: S aureus was cultivated from lesional skin of 22 of 25 patients with AD and 15 of 25 patients with PS. Isolated strains were toxigenic in 44% for patients with AD and in 36% for patients with PS. The activity of disease in AD and PS according to the Severity Scoring of Atopic Dermatitis (SCORAD) or Psoriasis Area and Severity Index score, respectively, correlated significantly (P = .001) with an isolated toxigenic strain in both diseases. S aureus from skin infections was toxigenic in half of the patients. All patients with erythroderma harbored S aureus, mostly on their skin. In AD, sepsis and skin infections, toxin C and in PS toxin B was most often detected. S aureus was cultured in 12% of healthy persons. These strains were toxin negative. The limitations of these investigations are that other potentially acting enterotoxins, such as toxic shock syndrome toxin-1, which may play a role in aggravating disease, were not investigated with our latex agglutination test.
CONCLUSION: In this study, S aureus was present in more than 50% of patients with AD and PS. We found that the severity of AD and PS significantly correlated to enterotoxin production of the isolated S aureus strains.TUMOR SUPPRESSOR PATHWAY J Cutan Pathol 2001;28:57-64
Presence of pathogenic T cells and associated chronic inflammation initially triggers a burst of proliferative activity by the basal layer and transiently amplifying keratinocytes
Once this occurs, keratinocytes in the suprabasal layers are triggered to undergo premature senescence by induction of p16
Once a chronic stable plaque is formed, progression to SCCA may be blocked by the p16 mediated tumor suppressor senescence switch
Research is directed at which T-cell derived cytokines are operative in the plaques and are responsible for the induction and persistence of lesional keratinocyte p16 expression
J Invest Dermatol 1991;97:672
Sceince 1990;247:205c-Fos expression is decreased in psoriatic lesions since one molecular marker for senescent cells is an inability to induce c-Fos after mitogenic stimuli
NF-kB PATHWAY Insulin-like growth factor II induces interleukin-6 expression via NFkappaB activation in psoriasis.
Kwon YW, Jang ER, Lee YM, Kim YS, Kwon KS, Jang HS, Oh CK, Kim KW.
Department of Molecular Biology, Pusan National University, Pusan, 609-735, Korea.
Biochem Biophys Res Commun 2000 Nov 19;278(2):312-7 Abstract quote
IGF-II is known to induce the growth of keratinocytes and the level was significantly elevated in the tissue fluid of psoriatic lesion. However, the role of IGF-II in psoriasis is not well defined. Because an inflammatory cytokine, interleukin-6 (IL-6) is overexpressed in psoriatic lesions, we explored whether IGF-II has some role in psoriasis through induction of IL-6.
Therefore, the expression of IL-6 was analyzed after treatment of IGF-II in primary cultured psoriatic cells and human keratinocyte cell line, HaCaT. We found that IGF-II induced the IL-6 mRNA expression significantly.
To investigate the inducing mechanism of IL-6 by IGF-II, we examined the promoter activity of IL-6 and the DNA binding activity of NFkappaB, a strong regulator of IL-6. Interestingly, IL-6 promoter activity and the binding activity of NFkappaB were remarkably increased by IGF-II. Western blot data that IkappaB was reduced by IGF-II significantly suggest that NFkappaB activation by IGF-II may be mediated through the downregulation of IkappaB.
Therefore, these results suggest a novel role of IGF-II in psoriasis possibly by inducing IL-6 through the activation of NFkappaB mediated by downregulation of IkappaB.
Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2.
Debets R, Timans JC, Homey B, Zurawski S, Sana TR, Lo S, Wagner J, Edwards G, Clifford T, Menon S, Bazan JF, Kastelein RA.
DNAX Research Institute of Molecular and Cellular Biology, 901 California Avenue, Palo Alto, CA 94304, USA
J Immunol 2001 Aug 1;167(3):1440-6 Abstract quote
IL-1 is of utmost importance in the host response to immunological challenges.
We identified and functionally characterized two novel IL-1 ligands termed IL-1delta and IL-1epsilon. Northern blot analyses show that these IL-1s are highly abundant in embryonic tissue and tissues containing epithelial cells (i.e., skin, lung, and stomach). In extension, quantitative real-time PCR revealed that of human skin-derived cells, only keratinocytes but not fibroblasts, endothelial cells, or melanocytes express IL-1delta and epsilon. Levels of keratinocyte IL-1delta are approximately 10-fold higher than those of IL-1epsilon. In vitro stimulation of keratinocytes with IL-1beta/TNF-alpha significantly up-regulates the expression of IL-1epsilon mRNA, and to a lesser extent of IL-1delta mRNA.
In NF-kappaB-luciferase reporter assays, we demonstrated that IL-1delta and epsilon proteins do not initiate a functional response via classical IL-1R pairs, which confer responsiveness to IL-1alpha and beta or IL-18. However, IL-1epsilon activates NF-kappaB through the orphan IL-1R-related protein 2 (IL-1Rrp2), whereas IL-1delta, which shows striking homology to IL-1 receptor antagonist, specifically and potently inhibits this IL-1epsilon response.
In lesional psoriasis skin, characterized by chronic cutaneous inflammation, the mRNA expression of both IL-1 ligands as well as IL-1Rrp2 are increased relative to normal healthy skin. In total, IL-1delta and epsilon and IL-1Rrp2 may constitute an independent signaling system, analogous to IL-1alphabeta/receptor agonist and IL-1R1, that is present in epithelial barriers of our body and takes part in local inflammatory responses.
LABORATORY/
RADIOLOGIC FINDINGSCHARACTERIZATION LIPID ABNORMALITIES
- Psoriasis is associated with lipid abnormalities at the onset of skin disease.
Mallbris L, Granath F, Hamsten A, Stahle M.
King Gustaf V Research Institute, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
J Am Acad Dermatol. 2006 Apr;54(4):614-21. Epub 2006 Jan 19. Abstract quote
BACKGROUND: Psoriasis appears to have increased cardiovascular morbidity. The underlying pathogenetic mechanisms remain unclear. Multiple factors, including systemic inflammation, oxidative stress, aberrant lipid profile, and concomitant established risk factors, have been discussed. However, previous studies consist of heterogeneous patient materials, including persons with highly varying disease duration and treatment.
METHODS: Two-hundred patients were investigated at the onset of psoriasis, comparing plasma concentrations of lipids, lipoproteins, and apolipoproteins with those of matched controls (N = 285).
RESULTS: Psoriasis patients manifest significant lipid abnormalities. Specifically, patients had significantly higher cholesterol concentrations in the very-low-density lipoprotein and high-density-lipoprotein fractions. Adjustment for established environmental risk factors did not affect the results.
LIMITATION: The response rate among control subjects was low. However, an additional analysis of a random subset of nonresponders demonstrated no substantial differences in the main results.
CONCLUSION: The study supports the notion that lipid abnormalities in psoriasis may be genetically determined rather than acquired.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION FACE
Facial psoriasis: Comparison of patients with and without facial involvement.
Young Park J, Hyun Rim J, Beom Choe Y, Il Youn J.
J Am Acad Dermatol. 2004 Apr;50(4):582-4. Abstract quote
BACKGROUND: Facial involvement in psoriasis has received little attention in standard descriptions of the disease because the face has long been thought of as rarely involved. A few reports have suggested that facial involvement might be a sign of severe psoriasis. However, there have been no comparison studies on the severity of psoriasis between patients with and without facial involvement.
OBJECTIVE: We sought to evaluate the prevalence and characteristics of facial involvement, and to compare the severity of psoriasis between the patients with and without facial psoriasis.
METHODS: A total of 282 consecutive patients with psoriasis seen in our psoriasis clinic between May 2002 and November 2002 were enrolled in this study.
RESULTS: Facial involvement was a marker of severe psoriasis. The face was often involved for patients with long duration or early onset of disease; with nail or joint involvement; and those requiring more extensive treatments. Patients with facial involvement were found to have more frequent pruritus, positive family history, and history of Koebner response.
CONCLUSION: Early recognition of facial psoriasis as a marker of severe disease can contribute to treatment of patients with psoriasis.PSORIATIC ARTHRITIS
- Diagnosis and treatment of psoriatic arthritis.
Mease P, Goffe BS.
Seattle Rheumatology Associates, Swedish Hospital Medical Center, Division of Clinical Research, WA 98104, USA.
J Am Acad Dermatol. 2005 Jan;52(1):1-19. Abstract quote
Psoriatic arthritis is a chronic, heterogeneous disease whose pathogenesis is unknown, although genetic, environmental, and immunologic factors play major roles. Psoriatic arthritis can follow an aggressive clinical course, and differentiating it from other arthropathies is sometimes difficult. Diagnosis of psoriatic arthritis is based on history, physical examination, the usual absence of rheumatoid factor, and characteristic radiographic features. At least 40% of patients with psoriatic arthritis develop radiographically detectable joint destruction; therefore, proper diagnosis and early treatment can have a significant impact on disease course and outcome.
Understanding the pathogenesis of psoriatic disease has led to the use of several biologic agents that work by modulating T-cell signaling or by inhibiting key cytokines involved in inflammation, such as tumor necrosis factor (TNF). TNF inhibitors have demonstrated excellent efficacy in resolving skin and joint disease in patients with psoriatic arthritis and have been shown to be safe agents in various inflammatory disorders. This article reviews the diagnostic and treatment challenges of psoriatic arthritis as they relate to pathogenesis and burden of disease.
LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should have acquired a more comprehensive knowledge of our current understanding of the classification, clinical presentation, etiology, pathophysiology, differential diagnosis, and treatment of psoriatic arthritis.
The clinical spectrum of psoriatic arthritis.Moll JM.
Clin Orthop 1979 Sep;(143):66-75 Abstract quote Epidemiologic, clinical, radiologic and serologic evidence suggests that psoriatic arthritis is a specific entity and not the coincidental occurrence of 2 common diseases, psoriasis and rheumatoid arthritis. Psoriatic arthritis may be defined as psoriasis associated with inflammatory arthritis (peripheral arthritis or spondylitis or both) and usually a negative serologic test for rheumatoid factor.
Clinical characteristics of the disease include: almost equal distribution between males and females; peripheral arthritis involving only a few small joints in asymmetical fashion; involvement of distal interphalangeal joints; sausage digits; arthritis mutilans; ankylosing spondylitis; goutlike onset; and higher frequency of nail involvement than occurs in uncomplicated psoriasis.
The rash may present with arthritis, or, equally, may precede or succeed joint involvement. With regard to pain and disability, the prognosis in psoriatic arthritis is better than in rheumatoid arthritis.
Psoriatic arthritis. Plain radiology and other imaging techniques.Porter GG.
Airedale General Hospital, Steeton, Keighley, West Yorkshire, UK.
Baillieres Clin Rheumatol 1994 May;8(2):465-82 Abstract quote The incidence of radiological change in psoriatic arthritis (PsA) is uncertain. The general pattern of the disease has been classified into five groups. This classification is still widely used, but recently a change of emphasis has been stressed in the classification and prevalence, particularly relating to the polyarthritic forms and the variability of symmetry and asymmetry.
The plain film findings in the axial and appendicular skeleton are described. In the former, bulky paramarginal ossification in the thoracolumbar spine is a prominent feature; destructive as well as ankylosing disease is seen in the cervical spine. In the latter, the key features are marginal erosions associated with proliferative new bone, acro-osteolysis, preservation of bone density, periostitis and bony ankylosis.
Progress of the disease is variable and, while the course is usually less severe than that in rheumatoid arthritis, progressive joint deformity occurs. Isotope scintigraphy is a useful technique for showing a general overview of joint involvement, but has limitations which impair its use in individual joints. CT is useful for looking at detailed bone anatomy and early demonstration of sacroiliitis. MRI may also be used to look at early sacroiliitis and has the potential for directly imaging the inflammatory process and the articular cartilage.
Radiological differentiation of PsA from other arthritides may be difficult, particularly in the early stages, and in oligoarticular disease. The differential diagnosis is discussed.
Treatment of recalcitrant psoriatic arthritis with anti-tumor necrosis factor-alpha antibody.Wollina U, Konrad H.
Department of Dermatology Dresden-Friedrichstadt, Germany.
J Eur Acad Dermatol Venereol 2002 Mar;16(2):127-9 Abstract quote Currently available treatments for psoriatic arthritis are either not completely effective or toxic in some patients. As tumour necrosis factor (TNF)-alpha is involved in both the joint and skin involvement in psoriatic arthritis, blockade of TNF-alpha seems a reliable way to treat patients with this disease.
We report two patients with progressive recalcitrant psoriatic arthritis treated with low-dose methotrexate (7.5 mg, once per week) in combination with intravenous chimeric monoclonal anti-TNF-alpha antibody (infliximab, 3 mg/kg body weight). Both showed a dramatic and rapid response in the reduction of pain, followed by improvement of laboratory and clinical signs of joint inflammation. Skin disease also responds after a short delay.
The observation shows that infliximab is effective and well tolerated in patients with recalcitrant progressive psoriatic arthritis. Different kinetics of symptom release during treatment suggest a variable role for TNF-alpha in disease pathways of pain, joint inflammation and skin involvement.
Diagnosis and management of psoriatic arthritis.Brockbank J, Gladman D.
Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, Toronto, Ontario, Canada.
Drugs 2002;62(17):2447-57 Abstract quote Psoriatic arthritis (PsA) is considered to be one of the spondyloarthritides, and as such has both spinal and peripheral joint involvement. In 80% of patients, psoriasis usually precedes the development of arthritis. Although there are no widely accepted diagnostic criteria, a number of distinct clinical features allow it to be distinguished from other forms of inflammatory arthritis.
It affects both sexes equally, and the pattern of joint involvement is characteristic with distal interphalangeal joint involvement, asymmetry, dactylitis, flail or ankylotic deformities of digits, and the frequent presence of enthesitis and spinal involvement.
It may have a pattern of joint involvement similar to rheumatoid arthritis (RA) but in these patients rheumatoid factor and the other systemic features of RA are usually absent. Radiographs frequently reveal evidence of asymmetric sacroiliitis and spinal disease, and peripheral joints, as well as showing erosions, may also demonstrate profuse new bone formation and ankylosis. Profound osteolysis producing the pencil-in-cup deformity can also occur in the same individual.
It is now recognised that PsA can be a destructive arthritis with an increased morbidity and mortality. Studies of standard disease-modifying therapies have been small and frequently inconclusive because of a high placebo response rate. This may be as a result of heterogeneity in patient selection, poor assessment tools, or the difference in underlying pathogenesis and subsequent response to therapy. In meta-analyses, sulfasalazine and methotrexate have been shown to be effective.
Treating the skin alone seems to have little impact on joint disease, and the relationship between skin and joints is still unclear. However, recent studies with anti-tumour necrosis factor agents, such as etanercept and infliximab, have shown considerable significant clinical benefit and provided the hope that we will at last have effective therapies for this disease.
Treatment of psoriatic arthritis and psoriasis vulgaris with the tumor necrosis factor inhibitor infliximab.Cauza E, Spak M, Cauza K, Hanusch-Enserer U, Dunky A, Wagner E.
Department of Internal Medicine V, Department of Rheumatology, Wilhelminenspital, Montleartstrasse 37, 1160 Vienna, Austria
Rheumatol Int 2002 Nov;22(6):227-32 Abstract quote OBJECTIVE. The aim was to evaluate the efficacy and safety of multiple infusions with achimeric, anti-tumor necrosis factor (TNF)alpha monoclonal antibody (infliximab) in patients with psoriatic arthritis (PsA) and psoriasis vulgaris.
METHODS. Over 22 weeks, nine patients with both active psoriasis and PsA received five infusions of 3 mg/kg infliximab. The endpoints included changes in the swollen and tender joints counts, American College of Rheumatology (ACR) preliminary criteria for improvement response rates 20, 50, and 70, and improvement in the psoriasis area and severity index (PASI).
RESULTS. The swollen count (SJC) and tender joint count (TJC) fell from means of 5.33+/-2.22 and 17.80+/-4.21 to 1.44+/-1.09 and 9.77+/-0.92, respectively, by week 2 ( P=0.02, P=0.02). This benefit was sustained through week 22 (2.00+/-1.12/7.77+/-3.68, P=0.05/ P=0.002). The ACR 20/50/70 response was achieved in 89%/56%/22% of cases. The mean PASI score improved from 19.04+/-5.41 to 4.91+/-2.51 ( P=0.002).
CONCLUSION. Multiple infusions of infliximab were effective and well tolerated in patients with active psoriasis and PsA.
PSORIASIS NAILS
Department of Dermatology, University of Toronto, Canada.
Psoriasis is a chronic skin disease that affects millions of people throughout the world. Even though cutaneous signs and symptoms are the most common clinical manifestations, the nails can be involved in up to 50% of cases, and their involvement remains an important yet often overlooked aspect of the disease. There is a broad spectrum of nail dystrophies associated with psoriasis, ranging from the common pitting and loosening of the nail plate to the less frequent discoloration and splinter hemorrhages seen in the nail bed.
This article discusses the normal anatomy and embryology of the nail unit as well as the current understanding of the pathogenesis of the disease. It also provides an extensive review of the existing literature with respect to psoriatic nail therapy. Although there have been many recent advances in the treatment of the cutaneous form of the disease-most notably in the field of immunotherapies-the options for nail psoriasis are far more limited.
While a number of treatment alternatives currently exist for nail disease, the general paucity of clear evidence regarding these choices often makes it difficult to select the most efficient, safe, and optimal treatment for the patient. Even though the current literature has shown some support for the use of topical, intralesional, radiation, systemic, and combination therapies for nail psoriasis, the available studies lack sufficient power to extrapolate a standardized therapeutic regimen.
Therefore, until better-documented evidence validating the treatment options emerges within the literature, clinicians and patients are left with a vague and relatively unproven approach to psoriatic nail disease.
Nail Psoriasis Severity Index: a useful tool for evaluation of nail psoriasis.Rich P, Scher RK.
Oregon Health Sciences University, Portland, OR 97210, USA.
J Am Acad Dermatol. 2003 Aug;49(2):206-12. Abstract quote The Nail Psoriasis Severity Index (NAPSI) is a numeric, reproducible, objective, simple tool for evaluation of nail psoriasis. This scale is used to evaluate the severity of nail bed psoriasis and nail matrix psoriasis by area of involvement in the nail unit.
The NAPSI will be useful during clinical trials for evaluating response to treatment of psoriatic nails. The scale is reproducible, and because there are few data points, statistical analysis is simplified.
PSORIASIS SCALP
Department of Pathology, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil.
In a study on scalp psoriasis of 19 patients (11 males and 8 females, 15-64 years of age, psoriasis area severity index partial score of the head ranging from 0.5 to 2.8), we came to notice that, apart from the classical criteria for the diagnosis of psoriasis which were present in all cases, in a majority of patients, sebaceous glands were extremely reduced in size.
We compared findings of follicular counts and sebaceous glands with a nonpsoriatic group of individuals (n = 26). Ten cases from the psoriatic population presented with completely atrophic glands, most of the time intermingled with larger glands (P = 0.03); not a single case showed sebaceous gland atrophy in the control group. There were no statistical differences regarding total number of hair follicles (P = 0.08), terminal follicles (P = 0.15), vellus follicles (P = 0.39), and telogen follicles (P = 0.58) between the groups. Other unusual features observed in the scalp psoriasis group were dilation of infundibula in 11 cases, a papillomatous epidermal surface in 8 specimens, parakeratosis at the lips of infundibular ostia in 8 specimens, mitotic figures in 7 cases, and necrotic keratinocytes in 14 cases.
We conclude that psoriasis of the scalp may present itself with unexpected microscopic findings, among them being atrophy of sebaceous glands. Further studies are necessary to clarify why this atrophy develops and if it is specific to psoriasis.PSORIATIC TENDINITIS
Achilles tendinitis in psoriasis: clinical and sonographic findings.De Simone C, Guerriero C, Giampietruzzi AR, Costantini M, Di Gregorio F, Amerio P.
Department of Dermatology, Universita Carrolica del Sacro Cuore, Rome, Italy.
J Am Acad Dermatol. 2003 Aug;49(2):217-22. Abstract quote BACKGROUND: Involvement of the Achilles tendon is frequent in psoriatic arthritis, but it is easily missed at clinical examination.
OBJECTIVE: To seek evidence of Achilles tendon abnormalities by means of sonography in psoriatic patients and to correlate sonographic findings with clinical symptoms (tendon and soft-tissue swelling, pain, and difficulty in walking).
METHODS: Fifty-nine patients with plaque-type psoriasis (Psoriasis Area and Severity Index score, 3.7-34.7) and 50 healthy, aged-matched volunteers underwent clinical and sonographic evaluation of Achilles tendons and peritendinous structures.
RESULTS: Eighteen (30.5%) of the 59 patients had clinical symptoms of Achilles tendinitis. Thirty-five (59.3%) of the patients had sonographic abnormalities. Of these, 13 patients had clinically symptomatic abnormalities, and 11 had psoriatic arthritis. Degenerative tendinitis was the most frequent sonographic finding (76.9%) among patients with symptomatic conditions. Five patients with symptoms did not have sonographic alterations. None of the controls had clinical or sonographic changes.
CONCLUSIONS: In psoriatic patients Achilles tendon abnormalities cannot be excluded even when they are clinically absent.SKIN VARIANTS GUTTATE More common in children
15% of cases
Erythematous papules 1-5 mm with a fine scale
Often preceded by streptococcal pharyngitis
TrunkJ Am Acad Dermatol 2001;44:433-8 Abstract quote
Case-control study
Cases were patients with a first diagnosis ever of acute guttate psoriasis, made by a dermatologist. Controls were patients newly diagnosed as having dermatologic conditions other than psoriasis and seen in the same outpatient services as the cases. Inclusion of cases and controls was restricted to patients older than 16 years. The Holmes and Rahe Social Readjustment Rating Scale was used to assess stressful life events during the 6 months before diagnosis. A total of 73 cases (median age, 26 years) and 430 controls (median age, 28 years) were included in the analysis.Results: A family history of psoriasis was strongly associated with guttate psoriasis, the multivariate odds ratio being 7.0 (95% confidence interval, 3.7-13.5) for subjects who reported a history of the disease in parents or siblings. Stressful life events were also associated with guttate psoriasis. The multivariate odds ratio was 1.7 (95% confidence interval, 0.8-3.6) for subjects scoring 41 to 100 and 2.6 (95% confidence interval, 1.3-5.2) for those scoring more than 100 on the Holmes and Rahe Scale. The risk increased with the reported history of any infectious disease. The analysis of specific diagnoses documented a high and significant association with acute pharyngitis, the adjusted odds ratio being 7.8 (95% confidence interval, 1.8-32.5).
Conclusion: The study confirmed that recent pharyngeal infection is a risk factor for guttate psoriasis. It also documented the strong association between guttate psoriasis and a family history of psoriasis. Finally, the study added evidence to the belief that stressful life events may represent risk factors for the onset of psoriasis. By relying on the clinical diagnosis we possibly underestimate the association of guttate psoriasis with infection.
ERYTHRODERMIC 2% of cases and 20% of erythroderma cases
Severe form may have high morbidity
May be precipitated by excessive use of steroidsErythrodermic psoriasis. Precipitating factors, course, and prognosis in 50 patients.
Boyd AS, Menter A.
Psoriasis Center, Baylor University Medical Center, Dallas, TX 75246.
J Am Acad Dermatol 1989 Nov;21(5 Pt 1):985-91 Abstract quote
Erythroderma represents the most severe form of psoriasis. In addition to its morbidity and severe discomfort, erythrodermic psoriasis also may be potentially life-threatening.
We present demographic, clinical, and laboratory findings of 50 patients with psoriatic erythroderma seen at our day-care center during a 9 1/2-year period. Precipitating factors included administration of systemic corticosteroids and the excessive use of topical steroids, phototherapy complications, severe emotional stress, and preceding illness. Treatment options are discussed on the basis of an average follow-up period of 34 months.
There appears to be a certain subgroup of patients with highly unstable psoriasis for whom appropriately planned therapeutic regimens are essential.
FOLLICULAR LINEAR PALMOPLANTAR
Palmoplantar lesions in psoriasis: a study of 3065 patients.Kumar B, Saraswat A, Kaur I.
Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Acta Derm Venereol 2002;82(3):192-5 Abstract quote Although palmoplantar psoriasis can be severely disabling, there are very few large clinico-epidemiological studies on this condition. Our purpose was to study the morphology and pattern of lesions in Indian patients with palmoplantar psoriasis and to elucidate the role of occupation in the incidence/localization of these lesions.
All patients attending our Psoriasis Clinic from 1993 to 2000 were screened for palmoplantar lesions and their demographic characteristics, occupation and the exact localization of the lesions were noted. Out of 3,065 patients screened, 532 had palm and/or sole involvement. Plantar lesions were seen in 91.9% and palmar lesions in 55.6% of these patients.
Four distinct patterns of lesion localization were noted on the palms and 5 patterns on the soles. Almost half of the men involved in regular manual labor had palmar lesions restricted to areas exposed to pressure, whereas only a quarter of other men had this type of lesion pattern. All patients with unilateral palmar lesions had them on their dominant hand and these patients were involved in regular manual labor.
In our patients, the prevalence of plantar lesions was much higher than that of palmar lesions. The possible role of occupational trauma in lesion localization in Indian patients with palmoplantar psoriasis is discussed.
PHOTOSENSITIVE PSORIASIS ALBA (INTERDIGITAL) Interdigital psoriasis (psoriasis alba): renewed attention for a neglected disorder.
Mommers JM, Seyger MM, van der Vleuten CJ, van de Kerkhof PC.
J Am Acad Dermatol. 2004 Aug;51(2):317-8.
Interdigital psoriasis ("white psoriasis").
WAISMAN M.
Arch Dermatol. 1961 Nov;84:73-40.
PSORIASIS SPINULOSA PSORIASIFORM NAPKIN DERMATITIS PUSTULAR PSORIASIS See file. SEBOPSORIASIS Yellow-red lesions over seborrheic portions of body VERRUCOUS Annular Verrucous Psoriasis With Exaggerated Papillomatosis
Emel Erkek, etal.
Am J Dermatopathol 2001;23:133-135 Abstract quote
Psoriasis is a disease of substantial clinical and microscopic diversity. We report a case of annular verrucous psoriasis associated with abnormal papillomatosis, resulting in finger-like projections.
We believe that this finding may represent another odd histopathologic feature in psoriasis with verrucous and rupial clinical morphology.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL Earliest stage, there may be vascular dilatation of the superficial papillary dermis associated with a mild perivascular dermatitis and spongiosis
Later, mounds of parakeratosis develop with neutrophils migrating through the epidermis
The fully developed lesion has mounds of parakeratosis containing neutrophils, hypogranulosis, increased mitotic activity within the epidermis, epidermal pallor, and areas of alternating orthokeratosis and confluent parakeratosis.
The epidermis is hyperplastic with regular elongation of the rete ridges associated with thinning of the suprapapillary plates.
Munro microabscesses and Kojog spongiform pustules may be present
As the lesions resolve, there are diminished inflammatory cells, less epidermal hyperplasia, but still capillary tortuosity.
VARIANTS ACITRETIN CHANGES
Department of Pathology, Hospital de Clínicas, Universidade Federal do Parana, Curitiba, Brazil.
BACKGROUND: Acitretin has been shown to be effective for psoriasis treatment. Its mechanism of action is not completely understood, and there are few studies focusing on histological and immunohistochemical differences before and after treatment of psoriasis with acitretin.
METHODS: This is a prospective study of 17 patients with plaque psoriasis treated with acitretin for 4 months with biopsies taken before and after therapy. Histological features and immunohistochemical reactions to cytokeratin (CK) 10, CK16, CK19, Ki67 and CD1a were evaluated and compared.
RESULTS: There were nine men and eight women with median age of 47 years. Epidermal thickness, CK16 positivity, Ki67 and CD1a-positive cell index reduced after treatment (p < 0.01). Suprapapillary plate thickness stayed the same (p > 0.05) although the epidermal/suprapapillary thickness ratio was significantly higher before treatment (p < 0.01). CK10 positivity was lower and a thicker basal cell layer was seen in the epidermis before treatment (p < 0.01). CK19 was negative in all cases.
CONCLUSIONS: Acitretin therapy improved histological and immunohistochemical features typical of psoriasis. In psoriasis, suprapapillary plates are not thin, but the epidermal/suprapapillary thickness ratio is increased. Basal cell layer is expanded in psoriasis. Langerhans' cells were less frequent after treatment, and that finding has to be investigated further to determine its role in acitretin mechanism of action.CYCLOSPORINE CHANGES
Sector of Dermatology and Post Graduation Course in Dermatology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Background: Cyclosporine is a potent immunosupressor, which induces cytokeratin expression pattern changes and dermal dendrocytes number increase.
Objectives: To evaluate its clinical effect in psoriasis, on keratinocytic proliferation and differentiation, and on dermal dendrocytes proliferation.
Methods: Thirty patients with psoriasis were treated and evaluated for 8 weeks. Clinical improvement was evaluated by Psoriasis Area and Severity Index (PASI). Biopsies were performed initially and after 8 weeks. Immunohistochemistry [CK markers 10, 14, and 16, and factor XIIIa+ (FXIIIa+)] was performed.
Results: Mean PASI before treatment was 26.32 and 3.71 after. Mean initial and final PASI difference was 22.61 (p < 0.001). Two patients had serum creatinine and six uric acid increase. Before and after treatment, mean numbers per field of dermal dendrocytes were 7.07 and 3.68, respectively. Mean difference was 3.39, with p < 0.001. CK10 immunohistochemical pattern demonstrated recovery of normal expression pattern in 26 patients, while CK14 pattern demonstrated improvement in 21 patients.
Conclusions: Cyclosporine was effective and safe for psoriasis in low doses, with significant decrease of PASI and dermal dendrocytes number after 8 weeks of therapy. CK10 and 14 pattern changed and, less prominently, CK16 expression. These modifications occur later than the PASI and dermal dendrocytes variation.VERRUCOUS
- Verrucous Psoriasis: A Distinctive Clinicopathologic Variant of Psoriasis.
Khalil FK, Keehn CA, Saeed S, Morgan MB.
From the *Department of Pathology, University of South Florida College of Medicine, Tampa, FL; daggerThe James A. Haley Veterans Hospital, Tampa, FL; and double daggerBay Area Dermatopathology Ameripath, Tampa, Florida.
Am J Dermatopathol. 2005 Jun;27(3):204-207. Abstract quote
Psoriasis is capable of presenting in a variety of clinical and pathologic guises including a rarely described variant variably termed hypertrophic or verrucous psoriasis.
Herein, we describe the clinical and pathologic attributes of a large series of patients with this unusual variant of psoriasis and distinguish it from other entities in the differential diagnosis.
The histopathologic features and clinical and demographic attributes of a series of 12 cases from 12 patients were reviewed by a single dermatopathologist (MM). The 12 patients consisted of 7 males and 5 females with an average age of 61.8 years (males 38-93 years, females 41-71 years). Eight of the patients were Caucasian, 3 Hispanic and 1 African-American. Six of the lesions were located on the knees, 4 involved the elbows, and 2 were seen on the dorsum of the hands (metacarpal-phalangeal joint). The clinical appearance of the lesions consisted of flesh-toned to white mammillated plaques (8 cases) and coalesced papules (4 cases).
Each of the biopsies showed regular psoriasiform epidermal hyperplasia with acanthosis, hyperkeratosis, and either spongiform neutrophilic or Munro micro-abscesses. In addition, each showed papillomatosis with bowing of the peripheral rete ridges toward the center of the lesion (buttressing).
At high power, epidermal neutrophils were seen in particular surmounting the tips of the suprapapillary plates with accompanying serum. Hypergranulosis and koilocytic change were not observed in any of the lesions. Human papilloma virus (HPV) immunostaining and periodic acid Schiff (PAS) special staining for fungi were negative. Verrucous psoriasis is a distinctive variant of psoriasis with overlapping clinical and pathologic features that might prompt consideration of verruca vulgaris. The presence of epidermal papillomatosis and epidermal buttressing seen in these lesions is reminiscent of the histologic features of verruca vulgaris. Similarly, the presence of coalesced papules might prompt clinical consideration of verruca vulgaris as well.
It is likely that this under recognized clinicopathologic entity represents a patterned response of the epithelium to repeated trauma/irritation typical of the anatomic locations that were encountered in this series. Recognition of this entity should preempt confusion with verruca vulgaris or other entities capable of producing wart-like epidermal changes.Annular Verrucous Psoriasis With Exaggerated Papillomatosis
Emel Erkek, etal.
Am J Dermatopathol 2001;23:133-135 Abstract quote
Psoriasis is a disease of substantial clinical and microscopic diversity. We report a case of annular verrucous psoriasis associated with abnormal papillomatosis, resulting in finger-like projections.
We believe that this finding may represent another odd histopathologic feature in psoriasis with verrucous and rupial clinical morphology.
Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008
Auspitz sign-Pinpoint bleeding when the psoriatic scale is removed.
Koebner phenomenon-New lesions developing at sites of trauma
Munro microabscesses-Intracorneal collections of neutrophils
Spongiform pustules of Kogoj-Intraspinal collections of neutrophils.
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