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INTRODUCTION Psoriasis is a chronic inflammatory skin disease that has a close relationship with genetic factors, characterized by complex changes in the growth and differentiation of various abnormalities and abnormal epidermal biochemistry, immunology, and blood vessels. Psoriasis is regarded as a primary disorder of keratinocytes. Has the form of a patch lesion demarcated erythema with rough scaly, multi-layered and transparent with wax drip phenomenon, and the phenomenon kobner Auspitz sign. 10 Psoriasis affects both sexes equally and can occur at any age, although it most commonly appears for the first time between the ages of 15 and 25 years. Psoriasis was first diagnosed before age 40 in 40% of patients with psoriasis. 2 Psoriasis can be classified according to the clinical picture, namely, guttate psoriasis, erythrodermic psoriasis, napkin psoriasis, inverse psoriasis, psoriasis arthritis, psoriasis vulgaris, pustular psoriasis and sebopsoriasis. 12 Psoriasis vulgaris is a chronic skin disease characterized by recurrent and presence of macular erythematous, round or oval shape can be covered scaly thick, transparent or grayish white. Smallsingle lesion might be confluent with firm boundaries resembles a map (psoriasis geographica). 11 It may be associated with other inflammatory disorders such as psoriatic arthritis, inflammatory bowel disease, and coronary artery disease. 7 1
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Page 1: Case Report Fix Print

INTRODUCTION

Psoriasis is a chronic inflammatory skin disease that has a close relationship with genetic

factors, characterized by complex changes in the growth and differentiation of various

abnormalities and abnormal epidermal biochemistry, immunology, and blood vessels. Psoriasis

is regarded as a primary disorder of keratinocytes. Has the form of a patch lesion demarcated

erythema with rough scaly, multi-layered and transparent with wax drip phenomenon, and the

phenomenon kobner Auspitz sign.10

Psoriasis affects both sexes equally and can occur at any age, although it most commonly

appears for the first time between the ages of 15 and 25 years. Psoriasis was first diagnosed

before age 40 in 40% of patients with psoriasis.2

Psoriasis can be classified according to the clinical picture, namely, guttate psoriasis,

erythrodermic psoriasis, napkin psoriasis, inverse psoriasis, psoriasis arthritis, psoriasis vulgaris,

pustular psoriasis and sebopsoriasis.12

Psoriasis vulgaris is a chronic skin disease characterized by recurrent and presence of

macular erythematous, round or oval shape can be covered scaly thick, transparent or grayish

white. Smallsingle lesion might be confluent with firm boundaries resembles a map (psoriasis

geographica).11 It may be associated with other inflammatory disorders such as psoriatic arthritis,

inflammatory bowel disease, and coronary artery disease.7

Psoriasis vulgaris is one of the most common inflammatory skin diseases among

Caucasians worldwide. With its early onset – usually between the ages of 20 and 30 – as well as

its chronic relapsing nature, psoriasis is a lifelong disease that has a major impact on affected

patients and society. Patients with psoriasis face substantial personal expense, strong

stigmatization, and social exclusion. Management of psoriasis includes treatment, patient

counselling, and psychosocial support.7 Nearly 30% of psoriasis patients have arthritis problems.

The onset of the disease occurs most commonly at about the age of 20 years. 10 to 15 % of

people have psoriatic arthritis.1

In the United States, about 7 million people (2%-3% of people) have psoriasis. About

150,000-260,000 new cases are diagnosed each year10. Most people who have psoriasis of the

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nails also have skin psoriasis (cutaneous psoriasis). Only 5% of people with psoriasis of the nails

do not have skin psoriasis. In people who have skin psoriasis, 10%-55% have psoriasis of the

nails (also called psoriatic nail disease). About 10%-20% of people who have skin psoriasis also

have psoriatic arthritis, a specific condition in which people have symptoms of both arthritis and

psoriasis. Of people with psoriatic arthritis, 53%-86% have affected nails, often with pitting.

Psoriasis tends to run in families. If you have a parent or a sibling who has psoriasis, you have a

16%-25% chance of having psoriasis, too. If both of your parents have psoriasis, your risk is

75%. Males and females are equally likely to have psoriasis. Psoriasis can occur in people of all

races.1

Psoriasis vulgaris with incidence in Western industrialized countries of 1.5% to 2%. In

more than 90% of cases, the disease is chronic. Patients with psoriasis vulgaris have a

significantly impaired quality of life. Depending on its severity, the disease can lead to a

substantial burden in terms of disability or psychosocial stigmatization. Indeed, patient surveys

have shown that the impairment in quality of life experienced by patients with psoriasis vulgaris

is comparable to that seen in patients with type 2 diabetes or chronic respiratory disease. Patients

are often dissatisfied with current therapeutic approaches, and their compliance is poor. Patient

surveys have shown that only about 25% of psoriasis patients are completely satisfied with the

success of their treatment, while over 50% indicate moderate satisfaction and 20% slight

satisfaction. The rate of non-compliance with systemic therapy is particularly high, ranging up to

40%.8

The prevalence of psoriasis is low in certain ethnic groups such as the Japanese, and may

be absent in aboriginal Australians2 and Indians from South America.6 Cause of psoriasis is still

unknown however, there are several factors such as : Genetic, inherited autosomal dominant with

incomplete penentrance and is associated with human leukocyte antigen (HLA)-B13, B17,

Bw57, Cw6, B27, and CW2. Immunologic factors, the genetic defect is expressed on T

lymphocytes, Langerhans cells, and keratinocytes. Several factors are thought to aggravate

psoriasis such as a streptococcal infected, stress, excessive alcohol consumption, and smoking.

Certain medicines, including lithium salt and beta blockers, have been reported to trigger or

aggravate the disease. Excessive alcohol consumption, smoking and obesity may exacerbate

psoriasis or make the management of the condition difficult. Individuals suffering from the

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advanced effects of the human immunodeficiency virus, or HIV, often exhibit psoriasis.

Sometimes food can also trigger the disease process. For e.g. citrus fruits, sour foods, sauces,

coffee, tea, alcohol and soft drinks.1

The diagnosis of psoriasis vulgaris is based almost exclusively on the clinical appearance

of the lesions. Auspitz’s sign (i.e. multiple fine bleeding points when psoriatic scale is removed)

may be elicited in scaly plaques. Involvement of predilection sites and the presence of nail

psoriasis contribute to the diagnosis. Occasionally, psoriasis is difficult to distinguish from

nummular eczema, tinea, or cutaneous lupus. Guttate psoriasis may resemble pityriasis rosea. In

rare cases, mycosis fungoides must be excluded. If the skin changes are located in the

intertriginous areas, intertrigo and candidiasis must be considered. In some cases, histological

examination of biopsies taken from the border of representative lesions is needed to confirm the

clinical diagnosis.8

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CASE REPORT

2.1. Identity Of Patient

Name : Mrs.K

Sex : Female

Registration number : 0-87-14-52

Age : 40 years old

Address : Ds. Blang Bintang

Occupation : Housewife

Examination Date : May, 26th 2014

2.2. Anamnesis

The Chief Complaint :

itching and red spots on the back of the left ear and body.

Additional Complaints :

Itchy on the lesion.

History of Present Illness :

The patient came to the clinic with complaints of itching and red spots on the back of the left ear and body since 3 years ago. In the first of the symptom start with a small of white lesion with the severe itching then the patient starching the lesion every time until the last year before she goes to polyclinic the lesion begin a red spot with the bigger plaque and much.

History of Previous Illness :

The patient admitted she had ever felt like this condition 8 year ago

History of Family Disease :

None of her family had the same disease or complaint like her.

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History of Treatment:

Last treatment on the polyclinic of dermatology dept (May 26th 2014)

Sistemik : Cetirizine 10 mg tab 1x1

Topical : 1. Asam salisilat 3% + LCD 5% + Dosoxicmetasone oint (morning-night)

2. Asam salisilat 3% + Diflucortolone valerate cream (afternoon)

3. Asam salisilat 3% + Vaselin album cream (night)

History of Social Habits :

The patient experiences stress in terms of its economy. Patient difficulties in

terms of school fees of his children.

2.3. Physical Examination

Vital Sign :

1. Blood pressure : 120/80 mmHg

2. Pulse : 80 beats/ minute

3. Respiratory Rate : 18 breaths/ minute

4. Temperature : 36,7˚C

Dermatological status :

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Figure 2.1 On regio posterior thoracalFigure 2.2 On regio ante bracii dextra and sinistra

Figure 2.1 At regio thorax posterior, erythematous plaques appeared, demarcated, irregular edges, the size of miliary up plaque, the number of multiple, over rough scaly lesions found generalized distribution.premises.

Figure 2.3 On regio extrimitas inferior

Figure 2.3 At regio extrimitas inferior, erythematous plaques appeared, demarcated, the number of multiple, irregular edges, the size of miliary up plaque, generalized distribution, and there is a scaling on it.

2.4 Resume :

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Figure 2.2 At regio extrimitas superior,

erythematous plaques appeared,

demarcated, irregular edges, the size of

miliary up plaque, the number of multiple

over smooth scaly lesions found

generalized distribution.premises.

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The Patient came to the clinic with complaints of itching and red spots on the back of the

left ear and body since 3 years ago. In the first of the symptom start with a small of white lesion

with the severe itching then the patient starching the lesion every time until the last year before

she goes to polyclinic the lesion begin a red spot with the bigger plaque and much. On

Dermatological status At regio thorax posterior, erythematous plaques appeared, demarcated,

irregular edges, the size of miliary up plaque, the number of multiple, over rough scaly lesions

found generalized distribution.premises. At regio extrimitas superior, erythematous plaques

appeared, demarcated, irregular edges, the size of miliary up plaque, the number of multiple over

smooth scaly lesions found generalized distribution.premises. And at regio extrimitas inferior,

erythematous plaques appeared, demarcated, the number of multiple, irregular edges, the size of

miliary up plaque, generalized distribution, and there is a scaling on it.

2.5 Differential Diagnosis :

1. Psoriasis Vulgaris

2. Tinea Korporis

3. Morbus Hansen Type TT

4. Pytriasis Rosea

5. Ekzema Seborrheic

2.6 Diagnose :

Psoriasis Vulgaris plaque type

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2.7 Planning :

Skin test :

- Kaarsvlek examination phenomen (+) : On examination karsvlek phenomenon in the

hands and feet be obtained which the positive

outcome when done scraping the lesions look

like a murky color was scrapings.

- Auspitz Sign Checks (+) : On examination Autspitz sign positive results which when

pursued scour the lesion seen on the bleeding point.

:

- Koebner examination (+) : On examination Koebner phenomenon also obtained positive

results when performed in which a healthy scratch on the skin

a few days later new lesions appear on the skin healthy.

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2.8 Management :

Sistemik :

- Cetirizine10 mg tab 1x1

Topical :

- Salicylic Acid 3% + LCD 5% (Carbonis Detegens Liquor) + Vaseline Album (Morning-

Night)

- Salicylic Acid 2% + Desoximethasone (Night)

2.9 Education :

1. Do not scrath the lesions

2. Consume the medicines according the doctor guideline

3. Keep the lesion area remains dry\

4. Maintain the cleanliness of the skin

5. Use clothes made of sweet arbsorbing material

3.0 Prognosis :

Quo ad vitam : dubia ad bonam

Quo ad Functionam : dubia ad bonam

Quo ad Sanactionam : dubia ad bonam

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DISCUSSION

The major manifestation of psoriasis is chronic inflammation of the skin. It is

characterized by disfiguring, scaling, and erythematous plaques that may be painful or often

severely pruritic and may cause significant. Psoriasis is a chronic disease that waxes during a

patient’s lifetime, is often modified by treatment initiation and cessation and has few

spontaneous remissions Inverse psoriasis is characterized by lesions in the skin folds. Because of

the moist nature of these areas, the lesions tend to be erythematous plaques with minimal scale.

Common locations include the axil-lary, genital, perineal, intergluteal, and inframammary areas.

Flexural surfaces such as the antecubital fossae can exhibit similar lesions.3

In case we find the patient with chief complaint Itch and red spots on the back of the left

ear and body. In the first of the symptom start with a small of white lesion with the severe itching

then the patient starching the lesion every time until the last month before she goes to polyclinic

the lesion begin a red spot with the bigger plaque. The patient admitted she had ever felt like this

condition 3 year ago.

Psoriasis is universal in occurrence however different population varies from 0.1 percent

to 11.8 percent. Psoriasis may begin at any age, but is uncommon under age 10 years. It most

likely appears 15-30 years. It certain HL-A CW6 antigen carier from family. Psoriasis is a

chronic inflammation skin deases with a strong genetic basic characteristic by complex dermal

growth epidermal diferentation and multiple biochemical, immunologic, vascular abnormality. It

caused poor keratinocyte.4 in case we find the lesion At regio thorax posterior, erythematous

plaques appeared, demarcated, irregular edges, the size of miliary up plaque, the number of

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Figure 3.1. Type the lesion of psoriasis

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multiple, over rough scaly lesions found generalized distribution.premises and on regio

extrimitas superior, erythematous plaques appeared, demarcated, irregular edges, the size of

miliary up plaque, the number of multiple over smooth scaly lesions found generalized

distribution premises and on regio extrimitas inferior, erythematous plaques appeared,

demarcated, the number of multiple, irregular edges, the size of miliary up plaque, generalized

distribution, and there is a scaling on it.

Initial lesion in the pin head sized macular lesion there marked edema, and monoclear

cell inflarates are found in the upper dermis. the overlying epidermis soon becomes spogiotic

with the focal loss of the granular layyer.5 Plaque psoriasis is the most common form, affect-ing

approximately 80% to 90% of patients. The vast majority of all high-quality and regulatory

clinical trials in psoriasis have been conducted on patients with this form of psoriasis. Plaque

psoriasis manifests as well-defined, sharply demarcated, erythematous plaques varying in size

from 1 cm to several centi-meters These clinical findings are mirrored histologically by

psoriasiform epidermal hyperplasia, parakeratosis with intracorneal neutro-phils, hypogranulosis,

spongiform pustules, an infiltrate of neutrophils and lymphocytes in the epidermis and dermis,

along with an expanded dermal papillary vasculature. Patients may have involvement ranging

from only a few plaques to numerous lesions covering almost the entire body surface. The

plaques are irregular, round to oval in shape, and most often located on the thorax posterior,

extrimitas superior and extrimitas inferior.3,5

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Depression/ suicide Psoriasis is associated with lack of self esteem and increased

prevalence of mood disorders including depression. The prevalence of depression in patients

with psoriasis may be as high as 60%. Depression may be severe enough that some patients will

contemplate suicide. In one study of 217 patients with psoriasis, almost 10% reported a wish to

be dead and 5% reported active suicidal ideation. Treatments for psoriasis may affect depression.

One study demonstrated that patients with psoriasis treated with etanercept had a significant

decrease in their depression scores when compared with control subjects. However, clinically

diagnosed depression was an exclusionary criterion for entry into this study.3 Therefore,

treatment of psoriasis with etanercept lessened symptoms of depression in patients without overt

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Figure 3.2 Picture of pathogenesis lesion on psoriasis5

clarification

1.Capillary dilatation increased the numbered of dermal mononuclear cells and mast cell. The process increase in epidermal thicknes

2.mast cell, macrophages, T cell (the component mediator inflamation)

3. lagerhan cell begin exit the idermis and inflamtory dendritic cell, cd8+ t cell begin to epidermal cell

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clinical depression. Increased rates of depression in patients with psoriasis may be another factor

leading to increased risk of cardiovascular disease. Although there is some suggestive evidence

that treatment of depression with selective serotonin reuptake inhibitors may reduce

cardiovascular events.3 In case the patient experiences stress in terms of its economy. Patient

difficulties in terms of school fees of his children. And when he getting start to remember she

difficulties in terms of school fees of his children always feel the symptom going severe, like itch

and red spot, in that case related with the literatur.

Obesity has become an epidemic within the United States. A body mass index (BMI) of

more than 30 is defined as obese with overweight being defined as a BMI between 25 and 30. In

the United States, 65% of people older than 20 years are either overweight or obese. Obesity has

serious health consequences including hypertension, vascular dis-ease, and type 2 diabetes

mellitus. Psoriasis was first associated with obesity in several large, European epidemiologic

studies. Studies from the United States also show an elevated BMI in patients with psoriasis.

These analyses of BMI compared subjects with and without psoriasis while controlling for age,

sex, and race. Analysis of data from the Utah Psoriasis Initiative revealed that patients with

psoriasis had a significantly higher BMI than control subjects in the general Utah population.3

The Nurses Health Study II, which contains prospective data from 78,626 women followed up

during a 14-year period, indi-cates that obesity and weight gain are strong risk factors for the

development of psoriasis in women. In this study, multiple measures of obesity, including BMI,

waist and hip circumference, waist-hip ratio and change in adiposity as assessed by weight gain

since the age of 18 years, were substantial risk factors for the development of psoriasis.

Multivariate anal-ysis demonstrated that the relative risk of developing psoriasis was highest in

those with the highest BMIs. In contrast, a low BMI (21) was associated with a lower risk of

psoriasis, further supporting these findings. Furthermore, the average weights of pa-tients with

psoriasis in the large clinical trials of the biologic agents have been in the 90- to 95-kg range

(although these clinical trials all enrolled more men than women) whereas the average body

weight for the US population from the NHANES database from1999 to 2002 was 86 kg. An

association between psoriasis and elevated BMI appears to be yet another factor that predisposes

individuals with psoriasis to cardiovascular disease.3 in that case the patient occurrence of obesity

with psoriasis vulgaris related with the literature, she have a BMI >30 that condition show she

get a obesity.

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From the history, physical examination, and investigation in this case , it can be enforced,

namely diagnosis of psoriasis vulgaris. Of history with the patient, obtained information which

led to the suspicion that the complaint psoriasis vulgaris lesions on the back of the left ear and

body since 3 years ago. Lesion area itchy and painful sometimes. Picture of psoriasis vulgarisis

characterized by slight itching, feels like summer. The most commonly affected areas are the

scalp, fingers and feet, palms of the hands, soles of the feet, umbilicus, gluteal, under the breasts

and genitals, elbows, knees, shins and sacrum. This disease is chronic in nature with a tendency

to relapse.1

Psoriasis vulgaris is a chronic skin disease characterized by recurrent and presence of

macular erythematous, round or oval shape can be covered scaly thick, transparent or grayish

white. Psoriasis vulgaris is recognized as the most common autoimmune diseases are caused by

the activation of the cellular immune system.7

Psoriasis affects both sexes equally and can occur at any age, although it most commonly

appears for the first time between the ages of 15 and 25 years. Psoriasis was first diagnosed

before age 40 in 40% of patients with psoriasis.8

Obtained from physical examination results reinforce plaque psoriasis vulgaris is looked

eriteumatous, demarcated, the number of multiple, irregular edges, plaque size, distribution and

generalized scaling above are his. Based on literature psoriasis is a chronic skin disease that is

characterized by recurrent and has patches demarcated lesions with erythematous scaly rough,

round or oval can be covered scaly thick, transparent or grayish white.8

The diagnosis of psoriasis vulgaris can be strengthened by the results of investigations

Karsvlek phenomenon/ phenomena spots where the wax when done scraping at the skin lesion

looks like a murky color wax scrapings. then forwarded scrapings and visible point on the lesions

that indicate bleeding Sign Auspitz positive. Then on healthy skin lesions arises when new

etching done the next day that signifies positive Koebner phenomenon.

By Wollf K 2012 investigation for the diagnosis of psoriasis vulgaris is a skin test that

consists of examination Karsvlek phenomenon (a phenomenon wax spots) are scaly psoriasis

when scraped muddy color will look like wax scrapings, Austpitz sign is when the way was for

warded to scrape visible point-point because of papillary dermis bleeding at the ends

ofelongated.

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Figure 3.3. Examination Austptiz Sign12

Koebner phenomenon, namely when the skin is exposed to trauma or scratching normally

will give rise to new lesions that are similar to those already existing.

Figure 3.4. Koebner phenomenon4

Other investigations such as histology, histologically, psoriasis has a marked thickening of

the epidermis appearance, due to the increased proliferation of keratinocytes in the epidermis and

undulations epidermal interfolikular into form very long, thin projections decline into the dermis.

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Figure 3.5 Psoriasis Preview Histopathology Vulgaris12

Mikroskoipic examination of psoriasis vulgaris11

1. Parakeratosis or hyperkeratosis,

2. Neutrophils in the stratum corneum or epidermis,

3. Benign epidermal,

4. Dilatation of the veins,

5. Elongation and enlargement of Paila dermis,

6. Thinning to loss granulalosum layer,

7. Munro Microabscess, an increase in the number of neutrophils in the stratum corneum cells.

In this case differential diagnosis of psoriasis vulgaris in this case are Tinea Corporis,

Morbus Hansen, Pytiriasis Rosea and Ekzema Seborrheic.because in terms of colored macular

erythematous lesions and have clinical symptoms of itching.

Management given to the patient in this case is cetirizine, salicylic acid 2% +

desoximethasone, salicylic acid 3% + LCD 5% (Liquor Carbonis Detegens) + Vaseline album.

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Therapy that can be administered in the form of topical treatment of psoriasis vulgaris as

corticosteroids once a day, plus vitamin D is applied once a day (applied separately, one in the

morning and the other in the evening) for up to 4 weeks as initial treatment for mild psoriasis.

Phototherapy, can use a narrow band ultraviolet B (UVB). Phototherapy is used for moderate or

severe psoriasis and people with plaque psoriasis or guttate-pattern resistant to topical treatment.

treatment with narrow band UVB phototherapy can be given 3 or 2 times a week.8

If the topical treatment and phototherapy cannot be resolved and in severe psoriasis can

be given systemic treatment such as methotrexate, cyclosporine.7

In this case given drugs such as cetirizine antihistamine to relieve itching. Salicylic acid

is given because it has keratolytic substances which have the effect of reducing the proliferation

of epithelial and keratolinisasi normalize impaired and at a concentration of 3% is used for

conditions keratolytic and hyperkeratotic dermatoses, desoximethasone given to patients with

psoriasis because it has anti-inflammatory and antiproliferative effects. LCD is one type of pitch

that functions as an anti-pruritic and increases keratinization normal.serta vaseline given to these

patients as a base for ointments.

REFERENCE

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1. Ashwin B. K, et al.Psoriasis: A comprehensive review. Int. J. of Pharm. & Life Sci.

(IJPLS), Vol. 2, Issue 6: June: 2011, 857-877 857.

2. Clinical practice Guidelines. 2013. Management of Psoriasis Vulgaris. Federal

Goverment Administrative Centre. Putrajaya. Malaysia.

3. Guidelines of care for the management psoriasis and psoriatic arthritis Section 1.

Overview of psoriasis and guidelines of for the treatment of psoriasis with

biologics Work Group: Alan Menter, MD, Chair, Alice Gottlieb, MD, PhD,

Steven R. Feldman, Abby S. Van Voorhees, MD, Craig L. Leonardi, MD,

Kenneth B. Gordon, , California; Birmingham, Alabama; and Cleveland, Ohio

2013.

4. James WD, Berger TG, Elston DM. Atopic Dermatitis, Eczema, and Noninfectious

Immunodeficiency Disorders. In : James WD, Berger TG, Elston DM, editors.

Andrew’s Disease of the skin : clinical dermatology. 11 th ed. Philadelphia:WB

Saunder Co;2011.p.62-87.

5. Johan E gundjonson james t elder Jean of Psoriasis In: Fitzpattrick’s Dermatology in

General Medicine 7thed. New York: Mc Graw Hill. 2008.p169 -171.

6. Langley, R.G.B, Krueger, G.G, Griffiths, C.E.M. Psoriasis: Epidemiology, Clinical

Features, and Quality of Life. Ann Rheum Dis 2005;64 (Suppl II) : ii18–ii23.

7. National Institute for Health and Clinical Excellence. 2012. The Assessment and

Management of Psoriasis.p.1-61.

8. Pathirana D, et all. 2009. European S3-Guidelines on the systemic treatment of

psoriasis vulgaris, Vol 23. European Academy of Dermatology and

Venereology.

9. Risdianto, A, et all. 2013. Tinea Corporis and Tinea Cruris caused by Trychophyton

Mentagrophytes Type Granular in Asthma Bronchiale Patient. Department

of Dermatovenereology Medical Faculty of Hasanuddin University, Wahidin

Sudiro Husod Hospital Makassar.

10. Setiawati S, Kadir D, Dewiyanti W dan Sungowati K. 2013. Psoriasis Vulgaris Treated

With Tropical Corticosteroid. Case Report Department of Dermatovenerology

Medical Faculty of Hasanudin University, Wahidin Sudiro Husodo Hospital

Makasar.

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11. Steven D, Billings and Cotton J. 2011. Inflamaotry Dermatopathology, Psoriasis

Vulgaris. Springer New York Dorddrecht Heidelberg London.

12. Wolff K., Johnson RA., Suurmond D. 2007. Fitzpatrick’scolor Atlas and Synopsis of

Clinical Dermatology 5th ed. New york : Mc Graw Hill Book Co.

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