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Pediatric Case = Conundrums Dr. Robert M. Lawrence University of Florida, Gainesville Saniyyah Mahmoudi, ARNP Carol M. Fulton, ARNP University of Florida,

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Presentation on theme: "Pediatric Case = Conundrums Dr. Robert M. Lawrence University of Florida, Gainesville Saniyyah Mahmoudi, ARNP Carol M. Fulton, ARNP University of Florida,"— Presentation transcript:

1 Pediatric Case = Conundrums Dr. Robert M. Lawrence University of Florida, Gainesville Saniyyah Mahmoudi, ARNP Carol M. Fulton, ARNP University 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 Objectives Present in a case-based discussion format –unique scenarios which highlight interesting concepts in Pediatric HIV care Utilization of Post-exposure Prophylaxis (PEP) Acute HIV Infection in a teenager Rheumatologic 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 years CD4 counts are stable @ 29-39% (765-1259) CDC Classification B3 – recurrent bacterial infections and CD4 % < 15% repeatedly @ 4 years of age History 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 normal Urinalysis shows + leukocyte esterase, 10 WBCs, 5 RBCs (subsequent culture + for Enterococcus >100,000 cfus) Positive Family History for “Rheumatoid Arthritis in the Paternal Grandmother Recent VL <50, CD4 28%, 966 Given Septra for UTI, and hydrocodone for hip pain

6 What is the most likely diagnosis at this time? 1.HIV-associated arthralgia / myalgia 2.Reactive Arthritis 3.Septic arthritis / osteomyelitis 4.Systemic Lupus Erythematosis

7 Rheumatologic Manifestations of HIV Infection Common Disorders HIV assoc. arthralgia/myalgia Reactive arthritis Psoriatic arthritis Vasculitis Polymyositis Pyomyositis Septic arthritis/osteomyelitis Zidovudine myositis Less Common Disorders Avascular necrosis Rhabdomyolysis Diffuse infiltrative lymphocytosis syndrome (DILS) Rheumatoid arthritis Systemic lupus erythematosis Sarcoidosis Reveille JD, Best Pract & Res Clin Rheumatology 20:1159-79, 2006 Colmenga I, Curr Opinion Rheumatology 18:88-95, 2 006

8 Case #1 This 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 stools She 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 sent Patient is given Naprosyn 375 mg PO BID, Prevacid f or symptomatic treatment

9 Arthritis of Left Knee

10 What is the most likely diagnosis at this time? 1.Rheumatic Fever 2.Reactive Arthritis 3.HIV associated Arthritis 4.Rheumatoid Arthritis 5.Systemic 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 #1 18 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, 2001 Palacios R et al. HIV infect and SLE. Lupus 11:60, 2002 Chang BG et al. Renal Manifestations of Concurrent SLE and HIV. Am J Kid Dis 33:441,1999 Haas M et al. HIV-associated IC glomerulonephritis with “lupus-like” Kidney Int 67:1381,2005 Chalom EC et al. Pediatric Pt. with SLE and congenital AIDS. Ped Rheum 6:7, 2008 Sacilooto NC et al. Juvenile SLE in a adolescent with AIDS Rev Bras Rheum 50:467, 2010

13 Case #1 This 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.

14 Lupus Nephritis WHO Class IV-G

15 Case #1 Take Home Points Musculoskeletal 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 HIV Cytotoxic agents can be used in refractory cases, with CD4 counts > 200.

16 Case #2 17 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 feet Patient reports unprotected receptive anal intercourse The 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 0.5-1 cm. red macules. His neurological exam is entirely normal.

17 What is the most likely diagnosis? 1.Syphilis 2.Chancroid (H.ducreyi) 3.LGV ( C. trachomatis) 4.Syphilis and GC 5.Syphilis and HIV

18 Clinical Picture of Primary HIV Infection Fever20 Lethargy12 Myalgia8 Headache8 Sore throat19 Inflammed throat 17 Coated tongue10 Enlarged tonsils9 Cervical LNs19 Axillary LNs 15 LNs at > 2 sites11 Rash15 Genital ulcer2 Anal ulcer2 Vomiting8 Nausea7 Diarrhea6 Weight loss > 5 kg4 Total # patients20 Incubation 11-28 days Gaines et al. BMJ 297:1363, 1988.

19 Exposure Risk (average, per episode, involving HIV-infected source) ExposureRisk 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 male 0.06% Female – female orogenital contact (only 4 case reports) IDU – needle sharing0.67% Perinatal (no prophylaxis)24% Verghese B et al. STD 2002;29:38-43. 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? 1.Yes 2.No 3.Abstain

21 HIV and Syphilis Is the LP indicated? CDC Guidelines Neurologic or ophthalmic signs or symptoms Evidence of active tertiary syphilis (aortitis, gumma or iritis) Treatment failure HIV infection with late latent syphilis or syphilis of unknown duration CDCP 2002 MMWR 51: 18-30 Other Criteria? 65 patients with neuorsyphilis and had LP 50/65 co-infected with HIV Plasma RPR >/=1:32 -- ~6x increased risk of neurosyphilis CD4+ count { "@context": "", "@type": "ImageObject", "contentUrl": "", "name": "HIV and Syphilis Is the LP indicated.", "description": "CDC Guidelines Neurologic or ophthalmic signs or symptoms Evidence of active tertiary syphilis (aortitis, gumma or iritis) Treatment failure HIV infection with late latent syphilis or syphilis of unknown duration CDCP 2002 MMWR 51: 18-30 Other Criteria. 65 patients with neuorsyphilis and had LP 50/65 co-infected with HIV Plasma RPR >/=1:32 -- ~6x increased risk of neurosyphilis CD4+ count

22 Case #2 Additional evaluation: No fluid in knees No other joints involved No penile discharge or “milkable discharge” No petechiae No epididymitis, proctitis or anal lesions No iritis or uveitis No known drug allergies Preliminary labs: BMP – WNL LFTs – WNL, except Tot. protein = 8.2g/dL WBC 6400 (69P/19L/7M/5E) Hgb =12.4 and Hct = 35.9 Platelets 268,000 Monospot negative Rapid Strep Test negative Rapid HIV1/2, Ab + Ag positive

23 Empiric STI Treatment with what? 1.Rochephin and Azithromycin 2.Wait for test results 3.Rochephin and Doxycycline 4.Rochephin, Azithromycin and Penicillin

24 Case #2 – One Week Later Signs and Symptoms Fevers, poor appetite Thin and pale Knees and ankle pain with early morning stiffness Weight loss 6 kg in 1 week No vomiting or diarrhea Penile lesion – flat hypopigmentation Rash – only peeling of palms and soles Diffuse lymphadenopathy Follow-up labs RPR 1:64, TPHA + HIV WB positive HIV RNA PCR = 240,000 GC cultures of urethra, rectum and throat all negative Urine GC / CZ NA are negative HIV Genotype pending No lymphocyte subsets

25 What would you like to do now? 1.Lumbar puncture and repeat Penicillin 2.Repeat Penicillin, discuss HIV 3.Recommend ARV Therapy 4.Refer to GI

26 Case #2 Ongoing Care - 8 weeks Treatment Completed three weekly IM injections of Benzathine PCN 2.4 million units Omperazole daily Naprosyn 500mg PO BID Nu-iron 150 mg PO BID MVI one tab PO BID Response No fevers, rashes 5 kg weight gain Only occasional joint pain or morning stiffness / no arthritis HLA B 27 positive RPR 1:16 Hgb 11.2 / Hct 33.8

27 Case #2 TimeCD4 Total (%) Viral LoadOther 0--240,000HIV Ag +, WB + 6 weeks359 (17%)395,430ARV naive 13 weeks221 (14%)193,887Genotype - pansensitive 18 weeks249 (16%)104,000 30 weeks191 (18%)123,000Atripla started 44 weeks396 (22%)66 Aggarwal M. Acute HIV Syndrome in an Adolescent. Peds 2003; 112:e323. Bell SK. Case 11-2009: 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 effusion No recent hospitalizations Immunizations UTD Lives with dad who is the primary caregiver h/o non compliance

29 DateMedicationsCD4 (absolute) Viral load 1/25/94-10/31/95Zidovudine 10/31/95-3/18/97Zidovudine, Didanosine 3/18/97-7/15/97Zidovudine, Lamivudine, Ritonavir (ACTG 338) 1/1/98-8/18/98Nelfinavir, Zidovudine, Epivir 490,641 8/18/98-1/5/99Zidovudine, Epivir, Amprenavir (GSK 141study) 1/5/99-12/28/99Stavudine,Didanosine, Amprenavir (GSK 141study) 12/28/99-2/25/03Stavudine, Epivir, Efavirenz 174-4012,439-10,965 2/25/03-6/24/03Didanosine, Stavudine, Lopinavir/r 401-35710,965-5,578 6/24/03-2/28/06Abacavir + Didanosine + Stavudine + Lopinavir/r 357-316 (132) 5,578 - <400 (117,000) 3/14/06-6/4/08Epzicom + Lopinavir/r + Stavudine 183-32912,400-1,580 8/1/08-9/27/10Truvada + Norvir + Atazanavir141-295520-9730

30 HIV GenoSURE 07/11/2006 Epzicom, Stavudine, Lopinavir/r

31 TRUGENE HIV-1 7/11/2007 Epzicom, Stavudine, Lopinavir/r

32 Phenotype 6/7/09 Truvada, Atazanavir/r

33 TRUGENE HIV-1 5/4/2009 Truvada, Atazanavir/r

34 TRU GENE HIV-1 7/26/10 Truvada, Atazanavir/r

35 Mutations RT mutations- 184V, T215Y/D, A62V PI mutations: L10I, M36I/V, I54M, D60E, L63, A71T, V77I, L90M

36 Mutation Interpretation PI Major Resistance Mutations: I54M, L90M PI Minor Resistance Mutations: L10I, A71T Other Mutations: M36IV, D60E, L63P, V77I

37 Mutation Interpretation NRTI Resistance Mutations: A62DV, M184V, T215DY NNRTI Resistance Mutations: None Other Mutations: None

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? He wants to take medications but is tired of taking so many pills 1.Take him off all HAART and start OI prophylaxis 2.Take him off all HAART, start OI prophylaxis, start 3TC 3.Start new regimen 4.Adherence counseling

40 What regimen options would you choose? 1. Atripla ® (efavirenz/tenofovir/ emtricitabine) + Raltegravir 2. Darunavir/r + Truvada ® (emtricitabine/tenofovir) + etravirine or raltegravir 3. Tipranavir/r + Truvada ® (emtricitabine/tenofovir) + etravirine or raltegravir 4. Send tropism assay for maraviroc

41 Current regimen Atripla ® (efavirenz/tenofovir/emtricitabine), raltegravir (CD4 at start-29) Continued dapsone/azithromycin One month and 3 months later: CD4 29 to 95 (10%), VL remains undetectable

42 Case # 4 20 yo with perinatal HIV infection Highly treatment experienced Currently on darunavir/r, raltegravir, emtricitabine/tenofovir, azithromycin, fluconazole, dapsone Remains noncompliant last VL >100,000, CD4 8 (1%) March of 2011 Ongoing issues: wasting (wt down to 94 lbs), diarrhea, candida esophagitis, pneumon ia

43 12/2009-11 pt was on atazanavir/r, raltegravir, emtricitabine/ tenofovir

44 1/2009-10 pt was on atazanavir/r, raltegravir, emtricitabine/ tenofovir

45 DateMedicationsCD4 (absolute) Viral loadMutations Mid 199970R, 67N, 98G 103N,219Q 2001 11yoZidovudine, Lamivudine, Abacavir, Nelfinavir 184V 2003 13 yoDidanosine, tenofovir, lopinavir/ritonavir 2006 16yo 315 (20%)308,000 2007 17yo 189 (15%)>750,000 11/2008 19yoAtazanavir/ritonavir, emtricitabine/tenofovir, raltegravir 22 (3%)461,000 2/2009 95 (8%)570 4/2009 44 (5%)1,690,000R41K, 164V 6/2010 to 10/2010 48 (7%) 6 (1%) 72,700 325,000 M36I HAART stop 3/20118 (1%)>100,000

46 What would you do next? 1.Take off HAART and continue OI prophylaxis only 2.Stress adherence and continue current HAART 3.Construct a new regimen 4.Take off HAART and start Epivir + OI prophylaxis

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