Genital Warts PDF

 GENITAL WARTS – VIRUS INFECTION BY HPV  AFFECTS BOTH THE SKIN AND MUCOSA  ANOGENITAL WARTS – INFECTION OF THE ANAL AND GENITAL MUCOSA AND THEIR ADJOINING AREA.  PREVALENCE –  OVER 50 % SEXUALLY ACTIVE ADULTS INFECTED WITH ONE OR MORE HPV TYPES  CAUSATIVE AGENT – HPV VIRUS ...

 GENITAL WARTS – VIRUS INFECTION BY HPV  AFFECTS BOTH THE SKIN AND MUCOSA  ANOGENITAL WARTS – INFECTION OF THE ANAL AND GENITAL MUCOSA AND THEIR ADJOINING AREA.  PREVALENCE –  OVER 50 % SEXUALLY ACTIVE ADULTS INFECTED WITH ONE OR MORE HPV TYPES  CAUSATIVE AGENT – HPV VIRUS  NAKED DOUBLE STRANDED DNA VIRUS  OF THE 100 GENOTYPES OF HPV – 45 GENOTYPES AFFECT GENITAL EPITHELIUM  BELONGS TO THE PAPOVAVIRIDAE FAMILY  NON ENVELOPED  72 PENTAMERIC CAPSOMERES  COAT CONSISTS OF MAJOR AND MINOR CAPSID PROTEINS ARRANGED ON A SKEWED ICOSAHEDRAL LATTICE  GENES DISTRIBUTED INTO EARLY ( E1 – E7 ) AND LATE ( L1 , L2 ) REGIONS  EARLY GENES ENCODE PROTEINS INVOLVED WITH REGULATION OF VIRAL DNA REPLICATION AND TRANSCRIPTION  LATE REGION L1 , L2 ENCODE FOR MAJOR AND MINOR CAPSID PROTEINS RESPECTIVELY  EARLY GENES E6, E7 INVOLVED IN ONCOGENIC TRANSFORMATION  HPV – EPITHELIOTROPHIC AND THEIR REPLICATION DEPENDS ON PRESENCE OF DIFFERENTIATING SQUAMOUS EPITHELIUM  VIRAL DNA BUT NOT STRUCTURAL CAPSID DETECTED IN LOWER LAYERS OF EPITHELIUM  CAPSID PROTEIN AND INFECTIOUS VIRUS + IN THE SUPERFICIAL DIFFERENTIATED LAYERS  VIRUS CANNOT BE GROWN IN VITRO  LOW-RISK HPV TYPES - 6 AND 11 CAUSE 90% OF EXTERNAL ANOGENITAL WARTS AND LOW-GRADE CHANGES IN CERVICAL CELLS.  OTHER LOW-RISK HPV TYPES - HPV 40, 42, 43, 44, 54, 61, 70, 72, AND 81.  HIGH-RISK TYPES 16 AND 18 - CAUSE INVASIVE CERVICAL CANCER.  HPV 16 - GREATEST ONCOGENIC POTENTIAL  OTHER ONCOGENIC HPV TYPES - 31, 33, 35, 45, 52, AND 58  GENITAL HPV – SEXUAL CONTACT  DURING SEXUAL ACTIVITY – MICROABRASIONS OCCUR IN THE GENITALIA  THESE MICROABRASIONS AND MOISTURE TRANSMIT HPV VIRIONS FROM THE EPITHELIAL CELLS OF THE INFECTED PARTNER TO THE BASAL LAYER OF THE RECIPIENT  DIGITAL TRANSMISSION  PERINATAL TRANSMISSION IN INFANTS BORN TO MOTHERS WITH GENITAL WARTS – THESE INFANTS DEVELOP LARYNGEAL PAPILLOMA AND CONGENITAL CONDYLOMA  BOTH CELL MEDIATED AND HUMORAL IMMUNITY INVOLVED  HUMORAL IMMUNITY –  ALMEDIA SHOWED ONE WAY CROSS REACTIVITY – CUTANEOUS WARTS AUTOINOCULABLE ON TO THE GENITAL MUCOSA , WHERE AS GENITAL WARTS DO NOT PRODUCE ANY LESION ON THE GLABOROUS SKIN  SERUM FROM PTS WITH CUTANEOUS WARTS INTERACT WITH ANTIGENS FROM CUTANEOUS AND ANOGENITAL WARTS WHERE AS SERUM FROM PTS WITH ANOGENITAL WARTS INTERACT WITH THE ANTIGENS OF ANOGENITAL WARTS ONLY  HUMAN SERA HAVE ANTIBODIES WHICH REACT TO THESE HPV PROTEINS  THOUGH CIRCULATING ANTIBODIES ARE SEEN IN PTS WITH WARTS , THEY DO NOT HELP IN THE ELIMINATION OF THE LESION OR IN PREVENTION OF RECURRENCES  IN PTS WITH REGRESSING WARTS – IgM ( 100 %), IgG (97%) , IgA ( 80 %) CLASS OF ANTIBODIES TO HPV ANTIGENS DETECTED  PRESENCE OF COMPLEMENT FIXING ANTIBODIES (IgG)+ - HIGH CURE RATE. IF CF ANTIBODIES ABSENT – SLOW HEALING PROCESS  INCREASE IN CMI - EFFECTIVE IN ELIMINATION AND PREVENTION OF RECURRENCE OF WARTS  DERMAL INFILTERATE OF MONONUCLEAR CELLS PRESENT AROUND SPONTANEOUSLY RESOLVING WARTS – ROLE OF CMI SUGGESTED  PRIMARY INFECTED CELLS IN WART NOT RECOGNISED BY THE IMMUNE SYSTEM DUE TO THE LOCAL INHIBITORY EFFECT OF THESE CELLS  THIS IS EVIDENCED BY ABSENCE OF LANGERHAN CELLS AND T CELLS IN THE EPIDERMIS SURROUDING THE WART IN COMPARISON TO THE NORMAL EPIDERMIS  ANTIGEN OF HPV SITUATED IN THE GRANULAR LAYER OF THE EPIDERMIS – THEREFORE THE EXPOSURE OF ANTIGEN TO THE IMMUNE SYSTEM IS HAMPERED AND THERE IS A DELAY IN THE DEVELOPMENT OF CMI.  HPV INFECTION AT THE BASAL CELL LAYER OF STRATIFIED SQUAMOUS EPITHELIUM STIMULATE CELLULAR PROLIFERATION IN EPITHELIUM AND INFECTED CELLS INTERACTION BETWEEN VIRAL PROTEINS AND CELLULAR PROTEINS ( ANTI ONCOPROTEINS ) THAT NORMALLY FUNCTION TO REGULATE THE CELL CYCLE SPECTRUM OF CHANGES FROM BENIGN HYPERPLASIA TO DYSPLASIA TO INVASIVE CANCER  E6 – DEGRADATION OF TUMOR SUPPRESSOR p53 , stimulates the expression of h TERT – THE CATALYTIC SUBUNIT OF TELOMERASE , AN ENZYME WHICH PROTECTS THE ENDS OF THE CHROMOSOMES  E7 – DEGRADATION OF RETINOBLASTOMA  IN BENIGN TYPE – VIRAL GENOME REPLICATES AS EXTRACHROMOSOMAL EPISOME  MALIGNANCY – VIRAL DNA IS INTEGRATED INTO THE CELLULAR CHROMOSOME  MAY REMAIN DORMANT WITHOUT PRODUCING ANY LESIONS OR MAY PRODUCE SYMPTOMATIC / ASYMPTOMATIC LESIONS SYMPTOMATIC LESIONS  APPEAR AFTER THE IP OF 1-8 MONTHS WITH AN AVERAGE OF 3 MONTHS  MEN MC SITE – INNER LINING OF THE PREPUCE , FRENULUM , GLANS , CORONAL SULCUS , URINARY MEATUS , PENILE SHAFT , SCROTUM  WOMEN MC SITES – POSTERIOR PART OF INTROITUS , LABIA , PERINIUM , PERIANAL AREA  LESIONS ON VAGINA , CERVIX – SUBCLINICAL INFECTION  MC PRESENTATION – VERRUCOUS PAPULES / PEDUNCULATED LESIONS THAT MAY COALESCE TO FORM VERRUCOUS PLAQUES / CAULIFLOWER LIKE GROWTHS  PINK AND PAINLESS  DEPENDING ON CLINICAL APPEARANCE , WARTS CLASSIFIED AS – CONDYLAMA ACCUMINATA PAPULAR WART VERRUCA VULGARIS / KERATOTIC FLAT TOPPED PAPULES BOWENOID PAPULOSIS  PEDUNCULATED MASSES (CAULIFLOWER LIKE ) WITH FISSURES AND IRREGULAR SURFACE  COLOUR – RED TO PINK OR WHITE  CHARACTERSITIC WARTY DIGITATIONS  SEEN IN MOIST PARTUALLY KERATINISED EPITHELIUM  NON PEDUNCULATED , HEMISPHERICAL OR DOME SHAPED MASSES  1-4 mm IN DIAMETER  LOCATED ON FULLY KERATINISED EPITHELIUM  FIRM PAPULAR LESIONS WITH SLIGHTLY ROUGH HORNY SURFACE WITH NO PEDICLE  SEEN ON DRY AREAS LIKE – SHAFT OF PENIS , OUTER ASPECT OF PREPUCE , LABIA MAJORA , PERINEUM  SESSILE WARTS – TINY LESIONS WITH NO HORNY SURFACE- SEEN ON FULLY KERATINISED EPITHELIUM  MACULAR / SLIGHTLY RAISED  DETECTED ON PARTIALLY / FULLY KERATINISED EPITHELIUM  VARIANT OF PAPULAR WART  HYPERPIGMENTED , DOME SHAPED , SMOOTH AND FLAT TOPPED PAPULES – SIZE OF WHICH IS AROUND 7mm  HISTOLOGICALLY – HIGH GRADE SQUAMOUS INTRAEPITHELIAL NEOPLASIA AND +VE FOR HPV 16 DNA  SITES – PENILE SHAFT , GLANS PENIS , LABIA MAJORA AND MINOR , INGUINAL FOLDS , PERIANAL REGION  HPV 16/11 , 16/18 , 31/33/53 RECENTLY DEMONSTRATED  BASED ON H/O EXPOSURE  CLINICAL APPEARANCE  HISTOLOGICAL APPEARANCE  SEROLOGY  SENSITIVE METHOD OF DETECTION OF HPV DNA – PCR  GEL ELECTROPHORESIS  RESTRICTION ENDONUCLEASE CLEAVAGE  VIRAL ANTIGEN IN STRATUM GRANULOSUM DECTECTED BY PEROXIDASE – ANTIPEROXIDASE TEST , INDIRECT IMMUNOFLOURESCENCE , INDIRECT IMMUNO ALKALINE PHOSPHATASE REACTION  HYPERKERATOSIS WITH VERTICAL TIERS OF PARAKERATOSIS  MODERATE GRANULOMATOSIS  KOLIOCYTES SEEN IN GRANULAR AND UPPER SPINOUS LAYER – KOLIOCYTES POSSESS SMALL ROUND DEEPLY BASOPHILIC FRAGMENTED ECCENTRICALLY PLACED NUCLEI SURROUNDED BY CLEAR HALO WITH PALE STAINING CYTOPLASM WITH IRREGULAR MARGINS  NUCLEI – ENLARGED , HYPERCHROMATIC  IRREGULAR ACANTHOSIS  PAPILLOMATOSIS  CONDYLOMA LATA OF SYPHILIS  NON VENEREAL TREPONEMATOSIS  HYPERTROPHIC VERRUCOUS TYPE OF GRANULOMA INGUINALE  TBVC  SKIN TAGS  MALIGNANCY  SMALL WARTS CONFUSED WITH - PPP , MC , FORDYCE’S SPOTS , CAPILLARY ANGIOMA , LP , FOREIGN BODY GRANULOMA  BENIGN TUMORS – NEUROFIBROMA , LIPOMA  A RESINOUS MATERIAL WITH PODOPHYLLOTOXIN , ALPHA PELTATUM , BETA PELTATUM  OBTAINED FROM AMERICAN PLANT PODOPHYLLUM PELTATUM AND P.EMODI , AN INDIAN PLANT WHICH GROWS IN THE FOOT HILL OF HIMALAYAS  MOA – INHIBITS MITOSIS AND CAUSES SWELLING AND NECROSIS OF THE CELLS  C/I IN PREGNANCY – FETAL DEATH AND ABORTIONS  SYSTEMIC ABSORPTION RESULTS IN RENAL TOXICITY , NEUROPATHY , COMA , HEPATOTOXICITY , GRANULOCYTOPENIA , THROMBOCYTOPENIA  APPLIED TO WARTS BY THE CLINICIAN USING COTTON TIPPED SWAB AFTER APPLYING VASELINE IN THE SURROUNDING SKIN  TOTAL AREA OF APPLICATION – 10 cm2 , TOTAL VOLUME SHOULDNOT EXCEED 0.5 ML  1ST APPLICATION - WAIT FOR 5 MIN AND THEN WASH OFF  SUBSEQUENT APPLICATION – WAIT FOR 20 MIN AND WASH OFF  IF WARTS PERSIST AFTER 6 SITTING – OTHER TREATMENT MODALITIES  PODOFILOX – 0.5 % SOLUTION / GEL PURIFIED FROM PODOPHYLLIN  SELF APPLICATION  STABLE SHELL LIFE. NEED NOT WASH AFTER APPLICATION  DOESN’T CAUSE SYSTEMIC TOXICITY  APPLIED WITH COTTON TIPPED SWAB / FINGER OVER WART TWO TIMES A DAY FOR 3 DAYS FOLLOWED BY 4 DAYS OF NO THERAPY  TOTAL OF 4 CYCLES  TOTAL AREA OF APPLICATION - 10 cm2 , TOTAL VOLUME – 0.5 ml IMIQUIMOD –  IMMUNE RESPONSE MODIFIER – INDUCES THE RELEASE OF CYTOKINES INCLUDING IFN GAMMA , TNF AND CERTAIN INTERLEUKINS BY PERIPHERAL BLOOD MONONUCLEAR CELLS AND LYMPHOCYTES  ACTS THROUGH TLR 7  5% CREAM APPLIED WITH FINGERS THREE TIMES A WEEK ( EVRY OTHER NIGHT ) UPTO 16 WEEKS  AREA WASHED 6-10 HRS AFTER THE APPLICATION  MC SIDE EFFECT – IRRITATION  CRYOTHERAPY –  SUITABLE FOR INTERNAL WARTS LIKE MEATAL WARTS  DO NOT REQUIRE ANAESTHESIA  TIP OF CRYOPROBE / SURFACE OF WART COVERED WITH KY JELLY BEFORE FREEZING  TWO SHORT FREEZE CYCLES EFFECTIVE  LIQUID NITROGEN  APPLIED BY PRESSING COTTON SWABS ON ORANGE STICKS DIPPED IN LIQUID NITROGEN ON THE WARTS AND HOLDING FOR A MINUTE  ALL PTS OFFERED FOLLOW UP EVALUATION AT 3 MONTHS AFTER TREATMENT ✓ IN MEN URETHRAL MEATAL LESION – OBSTRUCTS THE FLOW OF URINE ✓ IN WOMEN LARGER WARTS – CERVICAL DYSTOCIA ✓ ULCERATION ✓ SECONDARY INFECTION ✓ HAEMORRHAGE ✓ GIANT CONDYLOMA – BUSCHKE AND LOWENSTEIN – HISTOLOGICALLY BENIGN (INTACT BASAL CELL LAYER ) CLINICALLY – LARGE FOUL SMELLING CAULIFLOWER LIKE MASSES , LOCALLY INVASIVE , DESTRUCTIVE AND NON METASTASIZING LESION - + HPV 6 DNA ✓ MALIGNANT TRANSFORMATION ▪ INCREASE IN NUMBER AND SZE ▪ DUE TO HORMONAL LEVEL , VASCULARITY , IMMUNODEFICIENCY ▪ EVEN WITHOUT TREATMENT – WARTS MAY RESOLVE AFTER DELIVERY ▪ NEWBORN PICK UP THE INFECTION – TO AVOID NEONATAL TRANSMISSION ELECTIVE LSCS ▪ TREATMENT – CRYOTHERAPY AND TCA , EXICISION OF LARGER WARTS  TWO PROPHYLACTIC HPV VACCINES AVAILABLE INTERNATIONALLY  BOTH PREPARED FROM PURIFIED L1 STRUCTURAL PROTEINS BY RECOMBINANT TECHNOLOGY.  THESE PROTEINS SELF-ASSEMBLE TO FORM VIRUS-LIKE PARTICLES (VLPS) THAT INDUCE A PROTECTIVE HOST IMMUNE RESPONSE.  COMPARED WITH IMMUNITY-ACQUIRED FOLLOWING NATURAL INFECTION, THE VACCINE-INDUCED IMMUNITY IS MUCH STRONGER, LONG LASTING, AND INCLUDES PARTIAL CROSS-PROTECTION TO NON- VACCINE-RELATED SEROTYPES. ▪ H/O SEVERE ALLERGIC REACTIONS AFTER A PREVIOUS VACCINE DOSE OR TO A VACCINE COMPONENT (YEAST ALLERGY FOR GARDASIL® , LATEX ALLERGY FOR CERVARIX™ PREFILLED SYRINGES). ▪ H/O ABNORMAL PAP SMEAR OR ANOGENITAL WARTS IS NOT A CONTRAINDICATION AND PAP SMEARS OR HPV TESTING ARE NOT REQUIRED PRIOR TO VACCINATION. ▪ SINCE VACCINES DO NOT CONTAIN LIVE BIOLOGICAL PRODUCTS OR VIRAL DNA, THEY ARE NON-INFECTIOUS. ▪ ADVERSE REACTIONS – PAIN AND ERYTHEMA AT THE INJECTION SITE ▪ PREGNANCY- CATEGORY B – BETTER TO BE AVOIDED