AIDP/CIDP Anal Pap Smear Jeffrey A. Beal, M.D. Faculty, Florida/Caribbean AIDS Education Training Center

III.35 AIDP/CIDP Discuss the clinical presentation, differential diagnosis, and management of acute and chronic inflammatory demyelinating polyneuropathy in HIV+ patients

III.16 Anal Pap Smears Describe an anal Pap smear, how it is performed, and its potential use for screening for anal intraepithelial neoplasia in men and women, and discuss indications for referral to a specialist for patients with abnormal Pap smears

Acute or Chronic Inflammatory Demyelinating Polyneuropathy (AIDP or CIDP) Demyelinating Polyneuropathies are diagnosed in 1/3 of HIV+ Patients referred for peripheral nerve disease Cause: autoimmune-induced inflammatory response and breakdown of peripheral nerve myelin HIV is now an important cause of inflammatory demyelinating neuropathies. Precise incidence is not known. IN the US, two studies demonstrate that Inflammatory demyelinating neuropathies are diagnosed in one third to HIV-seropositive patients referred for peripheral nerve diseases. CIDP was more frequent than AIDP in 2 European and North American reports while AIDP was more common in African patients. The mild sensory involvement differentiates this neuropathy from HIV related sensory neuropathies.

Acute or Chronic Demyelinating Polyneuropathy (AIDP or CIDP) Rapid onset and progression Often develops during HIV seroconversion or during early HIV infection CIDP More common in middle to late stages of HIV disease Slower onset and progression over several weeks or months AIDP is Gullain-Barre’ Syndrome. It progresses over days to less than 4 weeks. CIDP can occur at any phase of HIV disease.

Acute or Chronic Demyelinating Polyneuropathy (AIDP or CIDP) Characteristic features: AIDP: Progressive ascending lower and upper extremity weakness, more distal than proximal CIDP: Patchy (can be both distal and proximal) lower and upper extremity weakness Respiratory paralysis in AIDP Cranial neuropathy (VII, X, XII) in both More distal weakness than proximal. CIDP can be both distal and proximal at presentation, patchy.

Acute or Chronic Demyelinating Polyneuropathy (AIDP or CIDP) AIDP & CIDP: Mildly impaired sensation, mild pain Autonomic dysfunction with cardiac arrhythmia, urinary retention, and blood pressure instability Hyporeflexia or areflexia Thomas, et. al.; eMedicine Journal, January 18, 2002, Vol. 3, No. 1

Acute or Chronic Demyelinating Polyneuropathy (AIDP or CIDP) CSF  increased protein with lymphocytic pleocytosis EMG and nerve conduction velocity studies show marked slowing of nerve conduction velocities and conduction block Nerve Biopsy macrophage-mediated segmental demyelination Lymphocytic pleocytosis (10-50 cells/mm3) distinguishes HIV-associated inflammatory demyelinating polyneuropathies from those present in noninfected patients. When found on CSF exam, it should prompt evaluation for HIV in AIDP or CIDP presentations where HIV status is not known. The EMG and NCV are critical for accurate diagnosis. NCV is diagnosis the disease. Nerve BX. Are not done any longer. If clinical and physiologic features are not typical, Nerve biopsy may be needed.

Acute or Chronic Demyelinating Polyneuropathy (AIDP or CIDP) Treatment of AIDP: Plasmapheresis or IVIG, not corticosteroids Concomitant GCV, FOS, or, Cidofovir if CD4 < 50 Treatment of CIDP Prednisone Intravenous immunoglobulin as effective as plasma exchange AIDP is usually treated with plasmapheresis or IVIG, NOT CORTICOSTEROIDS. If CD4 < 50 cells/mm3 treatment for CMV with ganciclovir, foscarnet, or cidofovir is advised. In CIDP, a randomized, controlled study has confirmed the benefit of tx. With prednisone. IVIG has also been shown to be effective and in one study it was as effective as was plasma exchnage. Plasmapheresis, 4-5 procedures over a 7-10 day period IVIG 2 g/kg IV over 2-5 days Prednisone 60-100 mg daily for several months or until clinical improvement; taper slowly to qod.

III.16 Anal Pap Smears Describe an anal Pap smear, how it is performed, and its potential use for screening for anal intraepithelial neoplasia in men and women, and discuss indications for referral to a specialist for patients with abnormal Pap smears

Anal Pap Smear The incidence of anal cancer among HIV infected MSM is higher than that among HIV-negative MSM Goedert JJ, Cote TR, Virgo P, et al. Spectrum of AIDS-associated malignant disorders. Lancet. 1998;351:1833-1839

Anal Pap Smear The incidence of anal cancer is also elevated among HIV-positive women compared to the general population. Frisch M, et.al, Human papillomavirus-associated cancers in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome. J Natl Cancer Inst. 2000; 92:1500-1510

Anal Intraepithelial Neoplasia “Left untreated, anal cancer is fatal. If detected at an early stage, however, survival is excellent among both HIV + and HIV – MSM. Like cervical cancer, anal cancer is probably preventable.” Screening for and Treatment of Anal Intraepithelial Neoplasia Joel Palefsky, MD HIV/AIDS Update 2002 MEDSCAPE 2002 Natural History

Anal Pap Smear Palefsky XIV AIDS Conf reported Prior to HIV, anal cancer incidence in MSM was 35 in 100,000 Since 1998 the risk has more than doubled and now exceeds the risk of cervical cancer in women Survey of >350 men in SF, anal swabs and anoscopy found early neoplasia in 52% Risk independent of CD4 and is not decreased with HAART

Anal Pap, Who to screen? MSM HIV infected women HIV infected Men with history of IDU Women with a history of high-grade CIN/cervical cancer or vulvar intraepithelial neoplasia/vulvar cancer Men and Women with history of perianal condlyoma Screening for and Treatment of Anal Intraepithelial Neoplasia Joel Palefsky, MD HIV/AIDS Update 2002 MEDSCAPE 2002

Anal Pap Smear Anal cytology sensitivity appears similar to cervical Pap smears, although the grade of dysplasia may not correlate as well with the histology The development of anal squamous intraepithelial lesion and invasive cancers of the anus generally occur at the level of the transformation zone, the area where the stratified squamous epithelium of the anus meets the columnar epithelium of the rectum. Anal cytology can detect the presence of abnormal cells that may be at risk for progression to cancer if untreated.

Anal Pap Smear Procedure: Moistened Dacron swab inserted 1-1.5” into anal canal Rotate swab and withdraw in a tight spiral motion. Sampling process of 15-20 seconds. Smear on glass slide and fix immediately or use Thin Prep liquid based media Sampling process should last between 15-20 seconds Thin Prep are less prone to drying artifact but initial studies reveal that traditional smear technique yields similar results. Darragh TM, Jay N, et al.  Comparison of conventional cytologic smears and ThinPrep preparations from the anal canal.  Acta Cytologica 1997; 41:4:1167-1170.

Anal Pap Smear No universally accepted guidelines Not yet considered Standard of Care Recommendations: Perform at initial exam and if normal, repeat in 6 months If initial 2 Pap smears are Normal, repeat annually. Consider more frequent when CD4 < 500 cells/mm3 Abnormal results refer for high-resolution anoscopy and biopsy For HIV + women and MSM

Anal Pap Smear Cost/Benefit Analysis: Screening q 2 years beginning during acute HIV infection hypothetical cohort HIV + MSM Cost of $13,000 per quality-adjusted life year Annual screening augmented this benefit at a cost of $16,000 per QALY saved TMP-SMX for PCP prophylaxis results in cost of $13,000 per year of life saved. Goldie, et.al.; May 19, 1999; JAMA Dr. Goldie and colleagues of the Harvard School of Public Health estimated the cost-effectiveness of anal cytology screening. QALY, or quality-adjusted life year refers to a year of life graded between 0.0 and 1.0 according to the type of ill health experienced during the year.

Anal Intraepithelial Neoplasia “Treatment of AIN has not been shown to prevent anal cancer. This is a serious impediment. Unfortunately, it becomes a self-fulfilling prophecy: we will not know until we try it. Cervical cytology screening was practiced for many years before it became clear that it was contributing to the reduction in cervical cancer incidence.” Screening for and Treatment of Anal Intraepithelial Neoplasia Joel Palefsky, MD HIV/AIDS Update 2002 MEDSCAPE 2002

III.35 AIDP/CIDP Discuss the clinical presentation, differential diagnosis, and management of acute and chronic inflammatory demyelinating polyneuropathy in HIV+ patients

III.16 Anal Pap Smears Describe an anal Pap smear, how it is performed, and its potential use for screening for anal intraepithelial neoplasia in men and women, and discuss indications for referral to a specialist for patients with abnormal Pap smears

High resolution anoscopy (culposcopy)