Presentation on theme: "Pediatric Case = Conundrums"— Presentation transcript:
1 Pediatric Case = Conundrums Dr. Robert M. LawrenceUniversity of Florida, GainesvilleSaniyyah Mahmoudi, ARNPCarol M. Fulton, ARNPUniversity of Florida, Jacksonville
2 Disclosure of Financial Relationships The speakers have no significant financial relationships with commercial entities to disclose.This slide set has been peer-reviewed to ensure that there are no conflicts of interest represented in the presentation.
3 ObjectivesPresent in a case-based discussion format –unique scenarios which highlight interesting concepts in Pediatric HIV careUtilization of Post-exposure Prophylaxis (PEP)Acute HIV Infection in a teenagerRheumatologic complications of HIV disease
4 Case #1 A 10 year African-American female with perinatal HIV infection On Epivir, Stavudine and Lopinavir/r for three + years.Viral load has been <50 for 3 yearsCD4 counts are 29-39% ( )CDC Classification B3 – recurrent bacterial infections and CD4 % < 15% 4 years of ageHistory of peripheral neuropathy – improved on Vitamin B6 50mg daily
5 Case #1!0 yo AA female present to the ER with pain in her left foot and left buttocks / hip without fever, gait reported as normalUrinalysis shows + leukocyte esterase, 10 WBCs, 5 RBCs (subsequent culture + for Enterococcus >100,000 cfus)Positive Family History for “Rheumatoid Arthritis in the Paternal GrandmotherRecent VL <50, CD4 28%, 966Given Septra for UTI, and hydrocodone for hip pain
6 What is the most likely diagnosis at this time? HIV-associated arthralgia / myalgiaReactive ArthritisSeptic arthritis / osteomyelitisSystemic Lupus Erythematosis
7 Rheumatologic Manifestations of HIV Infection Less Common DisordersCommon DisordersAvascular necrosisRhabdomyolysisDiffuse infiltrative lymphocytosis syndrome (DILS)Rheumatoid arthritisSystemic lupus erythematosisSarcoidosisHIV assoc. arthralgia/myalgiaReactive arthritisPsoriatic arthritisVasculitisPolymyositisPyomyositisSeptic arthritis/osteomyelitisZidovudine myositisReveille JD, Best Pract & Res Clin Rheumatology 20: , 2006Colmenga I, Curr Opinion Rheumatology 18:88-95, 2006
8 Case #1This 10 year old AA female returns 6 weeks later complaining of different joint pains, especially the left knee > right knee, no dysuria, no fevers, a 3 pound weight loss, and occasional loose stoolsShe has a red, warm, swollen left knee > the simply swollen right knee and decreased ROM of wrists and ankles due to pain not weakness (no “arthritis”)Rapid Strept throat swab + culture, urinalysis and culture, stool cultures, Urine for GC/CZ, ASO, PCR for CMV, EBV, HBV, HCV, HTLV-I and Parvovirus, along with a Rheumatologic panel and routine HIV labs are sentPatient is given Naprosyn 375 mg PO BID, Prevacid for symptomatic treatment
10 What is the most likely diagnosis at this time? Rheumatic FeverReactive ArthritisHIV associated ArthritisRheumatoid ArthritisSystemic Lupus Erythematosis
11 Case #1 All the “reactive arthritis” labs are negative. Her VL is <50 and CD4 counts are stable.The ANA is positive 1:1280. The RNP, SSA and SSB, Smith Ab, Anti-phospholipid Ab and Histone Ab are all positive with normal C3 and C4 levels.The tentative diagnosis is drug mediated autoimmune antibody response (Kaletra). Pt. continues on Prevacid, Indocin, and ASA with symptomatic relief.Her ARVs are changed based on Genotype testing and she intermittently has VL < 50 due to poor compliance.She is followed by the Rheumatology and ID services.
12 Case #118 months later this 12 yo female develops hematuria and proteinuria along with very low C3 and C4 levels and “re-elevation” of her autoimmune antibodies (ANA again 1:1280)A renal biopsy shows diffuse proliferative immune complex (IgG, IgM, C3 and C1q) glomerulonephritis, most consistent with lupus nephritis, Class IV-G.Mialou V et al. Lupus Nephritis in a Child with AIDS. Am J Kid Dis 37:E27, 2001Palacios R et al. HIV infect and SLE. Lupus 11:60, 2002Chang BG et al. Renal Manifestations of Concurrent SLE and HIV. Am J Kid Dis 33:441,1999Haas M et al. HIV-associated IC glomerulonephritis with “lupus-like” Kidney Int 67:1381,2005Chalom EC et al. Pediatric Pt. with SLE and congenital AIDS. Ped Rheum 6:7, 2008Sacilooto NC et al. Juvenile SLE in a adolescent with AIDS Rev Bras Rheum 50:467, 2010
13 Case #1This patient is now almost 16 years old with reasonable control of her Lupus nephritis and arthritis with monthly infusions of corticosteroids and cytoxan.Her medical care has been complicated by the separation and divorce of her parents.Her HIV is poorly controlled due to non-compliance with her ARV regimen.
15 Case #1 Take Home PointsMusculoskeletal disease in association with HIV is more common.Rheumatologic disease is also more common.Effective ARV therapy / control is an important aspect of therapy for these patients.Corticosteroids is the mainstay of therapy in most rheumatologic disease with HIVCytotoxic agents can be used in refractory cases, with CD4 counts > 200.
16 Case #217 yo WM presents to the ER with fevers, decreased energy and whole body aches for 2 weeks, diarrhea and 3 lb. weight loss in the last week, arthalgia in lower extremities, a new rash on hands and feetPatient reports unprotected receptive anal intercourseThe patient has a 1.5 cm “painless” ulcer on the corona of his penis. Temperature is 38.8 C. Both knees are swollen , warm but not red. His tonsils are 2+ without exudate or other oral lesions noted. There are multiple, bilateral 1-2cm. anterior cervical nodes which are mildly tender and non-tender 1 cm. inguinal LNs. His palms and soles have multiple cm. red macules.His neurological exam is entirely normal.
17 What is the most likely diagnosis? SyphilisChancroid (H.ducreyi)LGV ( C. trachomatis)Syphilis and GCSyphilis and HIV
18 Clinical Picture of Primary HIV Infection Fever 20Lethargy 12Myalgia 8Headache 8Sore throat 19Inflammed throat 17Coated tongue 10Enlarged tonsils 9Cervical LNs 19Axillary LNs 15LNs at > 2 sites 11Rash 15Genital ulcer 2Anal ulcer 2Vomiting 8Nausea 7Diarrhea 6Weight loss > 5 kg 4Total # patients 20Incubation daysGaines et al. BMJ 297:1363, 1988.
19 Exposure Risk (average, per episode, involving HIV-infected source) Percutaneous (blood)0.3%Mucocutaneous (blood)0.09%Receptive anal intercourse1%Insertive anal intercourse0.06%Receptive vaginal intercourse0.1 – 0.2%Insertive vaginal intercourse0.03 – 0.14%Receptive oral sex with a maleFemale – female orogenital contact(only 4 case reports)IDU – needle sharing0.67%Perinatal (no prophylaxis)24%Verghese B et al. STD 2002;29: European Study Group BMJ 1992;304:809.Macaluso JM et al. STD 1999;26:450-8.
20 Should you do an LP on this patient looking for Neurosyphilis? YesNoAbstain
21 HIV and Syphilis Is the LP indicated? CDC GuidelinesOther Criteria?Neurologic or ophthalmic signs or symptomsEvidence of active tertiary syphilis (aortitis, gumma or iritis)Treatment failureHIV infection with late latent syphilis or syphilis of unknown durationCDCP 2002 MMWR 51: 18-3065 patients with neuorsyphilis and had LP50/65 co-infected with HIVPlasma RPR >/=1: ~6x increased risk of neurosyphilisCD4+ count </= 350 cells -- 3x increased riskBoth parameters ~ 18x riskMarra CM 2004 JID 189:369
22 Case #2 Additional evaluation: Preliminary labs: BMP – WNL LFTs – WNL, except Tot. protein = 8.2g/dLWBC 6400 (69P/19L/7M/5E)Hgb =12.4 and Hct = 35.9Platelets 268,000Monospot negativeRapid Strep Test negativeRapid HIV1/2, Ab + Ag positiveNo fluid in kneesNo other joints involvedNo penile discharge or “milkable discharge”No petechiaeNo epididymitis, proctitis or anal lesionsNo iritis or uveitisNo known drug allergies
23 Empiric STI Treatment with what? Rochephin and AzithromycinWait for test resultsRochephin and DoxycyclineRochephin, Azithromycin and Penicillin
24 Case #2 – One Week Later Follow-up labs Signs and Symptoms Fevers, poor appetiteThin and paleKnees and ankle pain with early morning stiffnessWeight loss 6 kg in 1 weekNo vomiting or diarrheaPenile lesion – flat hypopigmentationRash – only peeling of palms and solesDiffuse lymphadenopathyRPR 1:64, TPHA +HIV WB positiveHIV RNA PCR = 240,000GC cultures of urethra, rectum and throat all negativeUrine GC / CZ NA are negativeHIV Genotype pendingNo lymphocyte subsets
25 What would you like to do now? Lumbar puncture and repeat PenicillinRepeat Penicillin, discuss HIVRecommend ARV TherapyRefer to GI
26 Case #2 Ongoing Care - 8 weeks TreatmentResponseCompleted three weekly IM injections of Benzathine PCN 2.4 million unitsOmperazole dailyNaprosyn 500mg PO BIDNu-iron 150 mg PO BIDMVI one tab PO BIDNo fevers, rashes5 kg weight gainOnly occasional joint pain or morning stiffness / no arthritisHLA B 27 positiveRPR 1:16Hgb 11.2 / Hct 33.8
27 Case #2 Time CD4 Total (%) Viral Load Other -- 240,000 HIV Ag +, WB + --240,000HIV Ag +, WB +6 weeks359 (17%)395,430ARV naive13 weeks221 (14%)193,887Genotype - pansensitive18 weeks249 (16%)104,00030 weeks191 (18%)123,000Atripla started44 weeks396 (22%)66Aggarwal M. Acute HIV Syndrome in an Adolescent. Peds 2003; 112:e323.Bell SK. Case : Case Records of MGH. NEJM 2009; 360:1540.
28 Case no. 3 17 yo male with perinatal HIV infection Past history significant for BOM with effusionNo recent hospitalizationsImmunizations UTDLives with dad who is the primary caregiverh/o non compliance
38 Mutation Interpretation M184V/I cause high-level in vitro resistance to 3TC and FTC and low-level in vitro resistance to ddI and ABC. M184V/I increases susceptibility to AZT, TDF, and d4T.T215Y causes AZT and D4T resistance and reduces susceptibility to ABC, ddI, and TDF particularly when it occurs in combination with M41L and L210W.T215S/C/D/E/I/V are transitions between wild type and the mutations Y and F.Other A62V is associated with multinucleoside resistance caused by Q151M; its effect in the absence of Q151M is not known.
39 What is the next best step What is the next best step? He wants to take medications but is tired of taking so many pillsTake him off all HAART and start OI prophylaxisTake him off all HAART, start OI prophylaxis, start 3TCStart new regimenAdherence counseling
40 What regimen options would you choose? 1. Atripla® (efavirenz/tenofovir/ emtricitabine) + Raltegravir2. Darunavir/r + Truvada® (emtricitabine/tenofovir) + etravirine or raltegravir3. Tipranavir/r + Truvada ® (emtricitabine/tenofovir) + etravirine or raltegravir4. Send tropism assay for maraviroc
41 Current regimenAtripla® (efavirenz/tenofovir/emtricitabine), raltegravir (CD4 at start-29)Continued dapsone/azithromycinOne month and 3 months later: CD4 29 to 95 (10%), VL remains undetectable
42 Case # 4 20 yo with perinatal HIV infection Highly treatment experiencedCurrently on darunavir/r, raltegravir, emtricitabine/tenofovir, azithromycin, fluconazole, dapsoneRemains noncompliant last VL >100,000,CD4 8 (1%) March of 2011Ongoing issues: wasting (wt down to 94 lbs), diarrhea, candida esophagitis, pneumonia
43 12/pt was on atazanavir/r, raltegravir , emtricitabine/ tenofovir
44 1/2009-10 pt was on atazanavir/r, raltegravir, emtricitabine/ tenofovir
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