Kaposi's sarcoma On Skin

Kaposi's sarcoma On Skin

dr. MOH. IFNUDIN, SpKK.

INTRODUCTION

Kaposi's sarcoma (SK) is a multifocal neoplasmik process arising from the endothelial cells of blood vessels and lymph vessels and particularly the blood vessels in the skin manifestations kulit.1 addition this disease can also in visceral organs. The disease is generally benign, rarely metastatic and non-fatal. But at a certain type of attack children in Africa and when accompanied by opportunistic infections can be fatal.

SK spread across dunia.2 Incidence in males was 30.1 per 100,000 and increased tenfold since the year 1950.3 In Uganda, the disease ranges from 48.9% of all malignancies in men laki3. In the United States this disease ranges from 48% in homosexuals with other State HIV.4 infections ever reported among other SK disease in Western Europe, Armenia, India, China and Jepang.5

SK exact cause is unknown, from the examination of the lesions by PCR found several types of viruses, bacteria and fungi that are suspected to cause disease. There are several predisposing factors are also considered to play a role Dalan fakro occurrence of this disease such as genetic, hormonal, oncogenes and immunosupresif. By not knowing the exact cause of the decree, the pathophysiology of this disease was not yet clear.

DEFINITIONS AND TYPE SK

SK is a multifocal neoplastic process arising from the endothelium of blood vessels and lymph vessels, especially blood vessels kulit.1

Is SK a malignant neoplasm or not still diperdebatkan.3 These two arguments each mempunayi good reason. Opinion that say that SK is not a true sarcoma has reason as follows:

1. Preview pathology in early lesions is a prominent component of inflammatory cells.

2. The absence of primary tumor (no spread from the primary).

3. The development of new lesions after several years always with clinical and histologic patterns of the same.

4. Tumors not bermetasis.

5. Tumors can regress spontaneously.

6. SK rarely causes death, and patients showed a normal life.

7. Only small tumors that developed into a presentation or stage anaplastic sarcomas.

While the opinion that said decree is a malignant neoplasm give the excuse that "there is an aggressive disease process in African children and men nomoseksual with DK" .5

SK divided into 4 types and 4 subtypes include:

1. Classical SK

2. Endemic SK consisting of:

a. Nodular type

b. Type anggresif

c. Type florid

d. Type limfadenopatik

3. SK associated with imunosupresiatrogenik.

4. SK epidemic (associated with HIV).

Epidemiology

SK widespread in the world, 2 but in all types mengenak generally more male than female.

1. Classical SK

Found in old male offspring Ashkenazic Jews in Eastern Europe and the Mediterranean.Usually occurs at age 50-80 years (average age 63 years). Comparison between patient male and female are 10-15: 1.

2. SK Endemic

Many are found in black men in Africa, especially in Zaire, Kenya, Tanzania, Rwanda, Zambia and Uganda. Occurs in adults aged 25-40 years (average age 35 years) and in children aged 2-15 years (average age 3 years). Comparison between patient male and female are 15-17: 1 and 3: 1.

3. SK associated with iatrogenic immunosuppression

In this type of people who are at risk of getting the patients receiving SK azatiprin therapy, cyclosporine and corticosteroids; patients receiving kidney trasnplantasi; patients with systemic lupus erythematosus and temporal arthritis. Occurred at the age between 20-60 years (average age 42 years). Comparison between patient male and female is 1.5 to 2.3: 1.

4. SK Epidemic

In this type more about male homosexuals is around 95% with age between 18-65 years (average age 37 years) and comparisons between men and women is 8: 1.

Etiology

SK could be due to a viral infection transmitted probably through sexual intercourse.Several viruses have been identified with the technique of polymerase chain reaction (PCR), among others:

a. Human herpesvirus 8 (HHV-8)

b. Cytomegalovirus (CMV) 3.5

c. Mycoplasma penetrans 3

d. HIV-1, 3

e. Human T-Cell Lymphotropic Virus Type 1 (HLTV-1) 3

Pathophysiology

SK pathophysiology is unclear, although the disease is thought to arise from viral infection, especially infection of HHV-8. Factors that may contribute Dalan SK emergence among others:

1. Genetic

Genetics may influence the development of this decree can be seen with increasing human liukocyte antigen (HLA) DRS in patients with classic type SK in Sadinia and Greece, in patients receiving kidney and bone marrow transplantation and in patients after receiving systemic corticosteroid therapy and also in AIDS patients with SK .5

2. Aspects of Hormone

Hormones are believed to influence the development of SK are:

a. Stimulate growth: dehidroepiandosteron and tertoteron. This is evidenced in a study in which HIV patients with SK has dehidroepiandosteron and tertoteron levels higher than HIV patients without SK. In the other study found that HIV patients treated with SK-alpha inerferon who experienced complete remission showed decreased levels of androgens during treatment.

b. Inhibits growth: beta-human chorionic gonadotropin (hCG) and estrogen (2-methoxyestradiol). Lunardhi and Alexander reported that in vitro generated human serum and mouse cells in early pregnancy inhibits Kaposi's sarcoma Y-1 (KS Y-1).Other researchers reported that sexual traits DK can be inhibited by hCG and in another study reported hCG injection produces complete regression of tumors in homosexuals with SK epidemic.

3. Immunosupresif

People with iatrogenic immunosupresif have a higher risk for malignancy.

4. Oncogene

The role of oncogenes in the pathogenesis of SK is indicated by:

• Discovery of K-rasoncogen changes in tumor specimens SK, I1-2, Oncostatin M and scatter factor receptors in SK cells.

• There is a scatter factor that causes changes in endothelial cells into spindle-shaped cells. It is also a mitogenic factor for SK cells in vitro.

• One study found that SK cells produce cytokines that autocrine and paracrine function.Cytokines produced include IL-1, IL-6, tumor necrosis factor (TNF) alpha, basic fibroblast growth factor (bFGF), vascular endothelial growth factor, platelet-derived growth factor (PDGF) and granulocyte macrophage-colony stimulating factor ( GM-CSF).

• In addition, factors that are also considered important in the growth of SK cells is intercellular adhesion molecule-1 and HIV tat proteins.

CLINICAL

1. Classical SK

• early form of macular lesions and patches of reddish, purplish or blackish brown, then lesions dilated and united to form plaque, a palpable tumor nodules and chewy and blackish or purplish color.

• Lymphoedema can be unilateral or bilateral.

• Lesions may leave scarring spontaneous remission of atrophy and hyperpigmentation.

• predilection foot and lower leg

• Lesions may spread sentripedal

2. SK Endemic

a. Nodular type

• Forms beruupa lesions papules and nodules that perkembangnannya slow.

• Predileksinya inferior extremity.

b. Type Aggressive

• shaped lesions eksofitik large nodules and tumor shaped like a mushroom.

• developments are fast and lesions can enter and damage the subcutaneous tissue and bone.

• Predileksinya extremities.

c. Type Florid

• Lesions shaped nodules very fast development.

• Predileksinya entire body surface.

3. Sk in patients with iatrogenic immunosupresif

• Lesions occur 2-8 months after therapy pertama.5 immunosupresif

• Lesions may regress in spontan.5

• The lesions patch, plaque and nodul.5

• Lesions may arise in the skin and visceral or developing more aggressive and can cause kematian.1

4. SK Epidemic

• Lesions first form of macular reddish or purplish, flat and fast developing into papules, nodules and plaques.

• palpable lesions, and does not itch does not dakit

• Lesions become sick if there is bleeding necrosis and lesions on the soles.

• Lymphederma in the inferior extremities.

• Predilekdinya in the face, neck, head, extremities and mucous membranes

• daapr regersi lesions sometimes spontaneously.

Histopathology

SK histopathologic picture is divided into three phases:

1. Phase Path

Reticular dermis little proliferation, irregular and scalloped round the vascular endothelium, normal adneksa structure; infiltrates of lymphocytes. Signs that stand out: the normal vessels or structures adneksa protruding into the gap ecstatic.

2. Phase plaque

Spindle cells extends along the irregular-shaped beam dermis collagen, cleftlike, looking blood vessels contain many red blood cells. There are core deposits and hyaline homosiderin that eosinifilik and infiltrates perivaskular.

3. Nodular phase

Sheets of spindle cells and sheets with soft to moderate cytologic atypia, nekronis single-cell, red blood cells trapped in slitelike extensive vascular network.

Diagnosis

Diagnosis based on history, clinical symptoms and histopathological examination.ELISA is necessary to know the HIV virus infection.

Differential diagnosis

SK must be distinguished from other diseases, namely:

1. Melanoma

• Symptoms: itching, irritation or pain.

• Lesions in the form of white spots, blue, brown or blackish, irregular and boundaryless firm.

• Microscopic: larger cells of nevus cells, irregular cell nucleus and the child prominent eosinophilic nucleus.

• Location: most of the lower limb, then the body, head, neck, upper extremities.

2. Angiomatosis basiler

• Symptoms: fever, malaise, weight loss and painful content.

• Etiology: Bartonella species.

• Lesions shaped red papules and subcutaneous masses noduler.

• Microscopic: non-neoplastic proliferation in skin blood vessels, glands linfe and visceral organs, neutrophil, the nucleus of dust and bacteria.

3. Dermatofibroma

• Symptoms: asymptomatic

• Lesions in the form of solid nodules are hard, sometimes in the ulcerative plaque berindurasi, typically arise in the body.

• Microscopic: neoplasm composed of fibroblasts with the preparation of the radial, epidermal thinning and often extend into subcutaneous fat.

• predilection: lower extremities, upper extremities and neck.

4. Hemangioma

• Symptoms: asymptomatic, arising from birth or a few days after birth ..

• Lesions in the form of patches of bright red or bluish, lobuler shaped, firm and hard limits on civilization.

• microscope kopis: proliferal endothelial cells in the dermis and / or subcutaneous tissue.

5. Granuloma anulare

• Symptoms: asymptomatic

• Lesions in the form: purplish erythematous or flesh-colored structured anular, murky or colored middle hyper - pigmentation.

• The lesions found in the back of his elbow and knee back foot.

• Lesions can heal itself.

MANAGEMENT

Although SK is a rare disease that threatens life, but the lesions do not pollute and harm that can cause physical and psychological stress.

Therapy can be administered locally or systemically and using a medicine or combination of drugs - drugs used include:

Systemic Therapy

1. Sistotoksik Therapy

a. Vinblastine

• How it works: vinblastine bound to tubulin and prevents meeting mikrotubuler component of the mitotic spindle, especially inhibit metaphase.

• Side effects: leukopeni, thrombocytopenia, anemia, paresthesias, loss of tendon reflexes, peripheral neuritis, mental depression, headeche, seizures, nausea, vomiting, stomatitis, glositis, constipation, ileus, plebitis, cellulitis, and alopecia.

• Indication: non-Hondgkin's lymphoma, choriocarcinoma, mammary carcinoma, neuroblastoma, head and neck cancer, cutaneous T-cell lymphoma, KS and hiticytosis X.

• Dose: 4-6 mg IV once a week.

• Dosage: 10 mg Powder

b. Vincristine

• How it works: Special to the M phase inhibit mitosis by blocking the metaphase through tubulin and microtubules prevented the meeting.

• Side effects: peripheral neuropathy, loss of tendon reflexes Achiles, paresthesias, foot drop, slaping gait, constipation, abdominal pain, ptosis, dipliopia, nausea, vomiting, alopecia, phlebitis and cellulitis.

• Indications: leukemia, lymphoma, sarcoma and carcinoma.

• Dosage: 2 mg IV 1-2 times a week.

• Dosage: solutio 1 mg / ml.

c. Bleomycin

• How it works: inhibits DNA synthesis.

• Indications: squamous cell carcinoma, malignant lymphoma, SK.

• Side effects: hypertension, swelling of fingers, palms hyperkeratosis, stomatitis, fever, headache, nausea, pulmonary fibrosis, alopecia.

• Dosage: 15 units of powder.

• Dose: 5 mg / d every 2 weeks 20 mg/m2/d civ X 3 d every 3 weeks.

d. Liposomal doxorubicin

• How it works: break the chains of DNA and destroy cells by free radicals.

• Side effects: tachycardia, arrhythmia, leveling the T wave, SY segment depression, leukopeni, stomatitis, esophagitis, alopecia.

• Indications: leukemia myelogen acute; disease Hodgkin's; aggressive non-Hodgkin's; serkoma, neuroblastoma; tumor Wilm's; carcinoma of the mammary, lung, stomach, pancreas, prostate, vesika urinaria, ovarian, endometrial, cervical, testicular and teroid; squamous cell carcinoma of the head and neck; hepatoma.

• Dosage: 20 mg/m2 every 3 weeks.

2. Biological Agent

a. Interfeon-alpha:

• How it works: influence cellular metabolism through changes in the cell nucleus.

• Properties: Antiviral, antiproliferasi, anti-inflammatory, immunoregulator.

• Side effects: fever, dry skin, lips and dry mouth, epistaxis, fatigue, nausea, anorexia, headache, atralgia, anemia, myalgia, lethargy, and neutropenia.

• Indication: non-Hodgkin's lymphoma, mycosis fungoides, KS, multiple myeloma, malignant myeloma, renal cell cancer, ovarian cancer, bladder cancer and chronic leukemia myelogenik.

• Dose: 20 MU IV / SC.

b. 9-cis retinoic acid (Alitretioin)

• How it works: SK inhibit cell proliferation by interleukin-6 (IL-6).

• Side effects: redness and skin irritation, pain, swelling, and paresthesias.

• Dosage: 60-100mg per oral.

c. Interleukin-12

• How it works: inhibit the angiogenic activity from the beginning of the induction of interferon-gamma (IFN-gamma) are alter-induced protein 10 (IP-10).

• Side effects: malaise, fever, nausea, vomiting, diarrhea, dyspnea, eosinophilia, anemia, fluid retention, increased bilirubin, increased serum creatinine, glositis, dry mouth, disorientation, psychosis, thrombocytopenia, erythema, hypotension, oliguric, alopecia and infarction infarction.

• Dosage: 100 mg / kg.

3. HIV-1 protease inhibitors:

a. Saquinavir

• Side effects: nausea, vomiting, diarrhea, hepatitis, lipodystrophy, hyperlipidemia, diabetes mellitus, hyperglycemia, headache, elevated liver enzymes.

• Dosage: 3 X 600 mg per day at meals or 2 hours after meals.

b. Ritonavir

• Side effects: nausea, vomiting, diarrhea, hepatitis, pancreatitis, hyperlipidemia, hyperglycemia, peripheral neuropathy, parastesia circumoral, asthenia, lipodystrophy, reduced soy sauce flavor, maculopapular rash, elevated liver enzymes, heat, hipermenore.

• Contra indications: This drug should not be used with the drug cisapride, terfenadine, astemizole, flecainide, midazolam, triazolam, and flurazepam. Beware of drug use terhadapt patients of chronic hepatitis B and hepatitis C chronic.

• Dosage: 2 X 600 mg per day at mealtime.

c. Indinavir

• Side effects: nausea, vomiting, diarrhea, hepatitis, nephrolitiasis, intertisial acute nephritis, acute renal failure, hyperglycemia, diabetes mulitus, hiperlipidemi, hemolysis, rash, lipodestrofi, headache, asthenia, blurred pandangnan, dizziness and feeling of metal.

• Contra indications: avoid use of antacids and medications with medication sucralfare.

• Dosage: 3 X 800 mg per day.

Combination therapy

1. Adriamycin 20 mg/m2 + Bleomycin 10 U/m2 + vincristine 2 mg every 2 weeks.

2. Interferon-alpha 15 million U / d + Zidovudine 600 mg / d.

Local Therapy

1. Sol. Vincristine 0.1 mg / ml intralesional every 2 weeks.

2. Sol. Alitretinoin 7% cream for 12-16 weeks.

3. Excision

4. Cryotherapy with liquid nitrogen

5. Laser

6. Radiation therapy dose of 800 cGy.

Prognosis

SK rarely cause death. Death can occur in cases of endemic type lymphadenopatic SK and the SK epidemic with opportunistic infections. Death in SK epidemic but not directly caused by infection oportunistiknya SK.

SK Survival varies for each type, namely:

1. Classical SK: The average survival of 10-15 years.

2. SK African endemic: an average 5 -8 year survival in adults and 1-3 years in children.

3. SK epidemic:

• Prognosis is good and the average survival reached 32 months when only a few lesions, new lesions appeared a few months, no history of opportunistic infection and CD4 cell count> 300/mm.

• Prognosis is poor and average survival of 7 months when developing an opportunistic infection within 3 months of diagnosis of SK.

SUMMARY

SK is a neoplasm of blood and lymph vessels are mainly on skin blood vessels. This disease does not have a clear etiology and patogenasis. Several factors such as genetic predisposition, hormonal, and oncogene immunosupresif allegedly involved in the occurrence of this disease.

SK affects more men than women. Prognosis depends on the type SK. The disease is generally benign, rarely metastatic and non-fatal, but this disease can be fatal when accompanied by opportunistic infections at the SK epidemic.

REFERENCES

1. Roan M, Mackie. Soft-Tissue Tumors. In: Champion RH, Burton JL, Burns DA, Breathnach SM, editors. Rook, Wilkinson, Ebling. Textbook of Dermatology, 6th ed.Oxfod: Blackwell Science Ltd., 1998. p. 2358-60.

2. Arnold HL. Odom RB, James WD. Andrew's Diseases of The Skin.8th ed.Philadelphia: WB Saunders, 1990.

3. Schwart RA. Kaposi's sarcoma: Advances and Perspectives. J Am Acad Dermatol 1996; 34: 804-10.

4. Pere Gascon, Schwart RA. Kaposi's Sarcoma: New Treatment Modalities.Dermatologic Clinics 2000; 18: 169-76.

5. Safai B, Wolfin N. Kaposi's Sarcoma-Acquired Immune Deficiency Syndrome in the Spectrum of Sexually Transmitted Diseases. In: Felman YM, Phil MM, editors. Sexually Transmitted Diseases. New York: Churchill Livingstone, 1986. p. 21-27.

Edting By: EnongXp