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Gonococcal Arthritis

Gonococcal Arthritis. Outline. Background Epidemiology Pathogenesis Clinical features Diagnosis Treatment/Resistance Summary. Background. Galen – 130 AD, “gonorrhea” Greek gonos (seed) and rhoea (flow) urethral discharge mistaken for semen Paris – Middle Ages

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Gonococcal Arthritis

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  1. Gonococcal Arthritis

  2. Outline • Background • Epidemiology • Pathogenesis • Clinical features • Diagnosis • Treatment/Resistance • Summary

  3. Background • Galen – 130 AD, “gonorrhea” • Greek gonos (seed) and rhoea (flow) • urethral discharge mistaken for semen • Paris – Middle Ages • house of prostitution known as “clapiers” • “clap” common name used • 18th century gonorrhea vs. syphilis? • Hunter’s experiment • Inoculated his urethra with pus from gonorrhea patient • Unfortunately patient had both • Developed chancers and concluded 2 diseases are same • Later presumably died from syphilitic aortic aneurysm

  4. Epidemiology • Colonize diverse mucosal surfaces • Most frequently reported communicable dz in US • Produce local and disseminated infections • DGI 0.5 to 3% of cases of mucosal infection • Most common cause of acute septic arthritis in young sexually active adults • Arthritis is most common complication

  5. Epidemiology • Prevalence greater in developing countries • 1975 peak 486/100k in US with decline 1995 149.5/100K • Increased incidence in: • Southern US states • Women • African Americans • Peak incidence in men 20-24 women 15-19

  6. GISP Annual Report 2006 www.cdc.gov - Gonococcal Isolate Surveillance Project

  7. GISP Annual Report 2007 www.cdc.gov

  8. GISP Annual Report 2006 www.cdc.gov

  9. GISP Annual Report 2006 www.cdc.gov

  10. Pathogenesis

  11. Pathogenesis • Risk factors • Women 3~4:1 • More often asymptomatic, delayed treatment, • Pregnancy and menses • Multiple sexual partners • Low socio-economic status • Non-caucasian • Previous gonorrhea infection • IVDU • HIV • Inherited complement deficiency (C5-9) • SLE

  12. Pathogenesis • Microbial factors • Pili • Outer membrane proteins: I (Porin), II, and III • 1A • Nutritional requirements (auxotyping) • AHU • Encapsulation • IgA proteases

  13. Microbial FactorsHochberg, Rheumatology, 4th edition

  14. Pathogenesis • Physical contact with mucosa • Highly infectious • 60-90% in females • 20-50% in males with single contact • Serum-sickness-like reaction • Vs. septic embolization • C5-C9 critical for lysis

  15. Immune Factors: Animal Models • Arthritis – unable to culture from symptomatic sites • Does not respond to steroids but to antibiotics • Perhaps can only recover bug in early phases • Is it an aseptic inflammatory response • Goldenberg et al. injected organism into rabbit knee resulted in synovitis but couldn’t recover organism • Also injected PCN-killed organism and LPS resulting in indistinguishable synovitis • Sterile microbial antigenic components involved?

  16. Clinical Features

  17. Gonococcal vs. Nongonococcal Adapted from: Rheumatology Secrets 2nd Ed. 2002 by S. West

  18. Clinical Features • Classification (controversial) • Arthritis dermatitis syndrome (aka bacteremic – 60%) • Fever, rash, tenosynovitis • Vs. Localized septic arthritis (40%) • Features of both, different stages of evolution?

  19. Clinical SpectrumHochberg, Rheumatology, 4th edition

  20. Clinical SpectrumHochberg, Rheumatology, 4th edition

  21. Clinical Features • Classic triad: • Dermatitis • Tenosynovitis • Migratory polyarthritis (polyarthralgias) • Initial manifestation, 1 d to 3 mo, or asymptomatic • Joint sx – peak within days

  22. Clinical Features • Dermatitis • 40-70% • Non-pruritic, painless • Tiny papules, pustules or vesicles with erythematous base, various states • Trunk, limbs • Sparing face and scalp • Resolve over 4-5 days without scarring • New lesions may appear after ABX

  23. SkinHochberg, Rheumatology, 4th edition

  24. Clinical Features • Tenosynovitis • 2/3, with or without joint involvement • Most common dorsum of hands, wrist, fingers, feet, ankles • Polyarthralgia/arthritis • >2/3, asymmetric, migratory • UE>LE • Peaks within few days • Small distal joints involvement****** • Rarely destructive • 1/3 spontaneously resolve

  25. Arthritis/Tenosynovitis Hochberg, Rheumatology, 4th edition

  26. Clinical Features - Other • Raremanifestations: pericarditis, endocarditis, perihepatitis, pyomyositis, osteomyelitis, meningitis

  27. Clinical Features • Raremanifestations: pericarditis, endocarditis, perihepatitis, pyomyositis, osteomyelitis, meningitis • Fitz-Hugh-Curtis syndrome – RUQ/upper belly pain/tenderness with friction rub

  28. Clinical Features • Rare manifestations: pericarditis, endocarditis, perihepatitis, pyomyositis, osteomyelitis, meningitis • Fitz-Hugh-Curtis syndrome – RUQ/upper belly pain/tenderness with friction rub • Waterhouse-Friderichsen syndrome – form of septicemia with shock, DIC, purpura, adrenal insuff., bilateral adrenal hemorrhage

  29. DDX • Non-gonococcal septic arthritis: • monoarticular, young and old, immunocompromised, prior joint damage, no dermatitis/tenosynovitis • Reiter’s: • less women, urethritis, conjunctivitis, arthritis, subacute, no fever, axial skeleton, hyperkeratotic lesions in palms and soles • Rheumatic fever: • follows strep infection, high fevers, marked systemic illness, rash, response to ASA or NSAIDs • Secondary syphilis: • rash on palms and soles • Hepatitis • SBE

  30. Secondary Syphilis

  31. Secondary Syphilis

  32. DDXUptodate, 2009 Adapted from UpToDate.com 2009

  33. Diagnosis

  34. Diagnosis • Fever, leukocytosis, elevated ESR, LFTs • Positive culture confirms diagnosis • Proven, probable, and possible based on culture • Proven <50%: blood, synovial fluid, skin lesions, or other sterile source • Probable: primary mucosal site, negative sterile site, clinical features • Possible: clinical features with expected response to therapy, negative cultures

  35. Diagnosis - Cultures • Synovial fluid culture • + <25% of time from purulent joints • Higher yield from primary mucosal site, 80% • cervical 90%, urethral 50-75%, pharyngeal 20%, rectal 15%) • Blood cultures 20-30% • Skin culture 5% • Check for Chlamydia, 30% association with Gc

  36. Diagnosis • Synovial fluid culture • + <25% of time • Higher yield from primary mucosal site, 80% • cervical 90%, urethral 50-75%, pharyngeal 20%, rectal 15%) • Blood cultures 20-30% • Skin culture 5% • Check for Chlamydia, 30% association with Gc DO MORE CULTURES!

  37. Diagnosis • Plate immediately, room temp • Chocolate agar (“dirty) or Thayer-Martin (or modified NY media; “clean”) “If it’s a clean site, use a dirty medium. If it’s a dirty site, use a clean medium.”

  38. Gram negative diplococciHochberg, Rheumatology, 4th edition

  39. Diagnosis • Antibody testing • <70% sensitive and <80% specific • Lower in asymptomatic patients than cultures • In low prevalence specificity unsatisfactory • PCR • 78-80% and 96-98% for sensitivity and specificity • Cannot test for antibiotic resistance and should not replace cultures.

  40. Treatment

  41. Treatment - Antibiotics • Hospitalization for initial therapy • Non-PCN Allergic: • First line = Ceftriaxone, 1 gram IM/IV q24h • Alt. = Cefotaxime or ceftizoxime 1 gram IV q8h • PCN Allergic • Spectinomycin 2 gram IM q12h, Cipro, Ofloxacin • Follow sensitivities • PCN Sensitive Organism? • PCN G, amox + probenecid, spectinomycin • Pregnant? • Ceftriaxone and Spectinomycin safe (Always consider checking IDSA or Sanford or CDC)

  42. CDC updated treatment recommendationMMWR, April 13, 2007 / 56(14);332-336

  43. Treatment - Duration • Continue IV 24-48 hrs after improvement begins • Then PO x at least 1 week • Cefixime 400mg po BID • Or Cipro 500mg po BID (contraindicated in children, pregnant, breast feeding) • All DGI get Chlamydia trachomatis treatment • Doxycycline 100mg BID x 7 days • Erythromycin 500mg daily x 7 days if pregnant • Sexual contacts need to seek evaluation • Consider checking beta-hCG in females!!

  44. Treatment • Synovial effusions • may require repeated aspiration • longer duration of ABX • open drainage rarely indicated • ABX into joint has no benefit • Recurrent DGI rare unless complement deficient • Repeat culture 5 days post ABX to ensure resolution

  45. GISP Annual Report 2007 www.cdc.gov

  46. Treatment Resistance • 2 mechanisms • chromosomal mutation • single step mutation, high pattern of resistance • mutation at several chromosomal loci, determine level and pattern of resistance • acquisition of plasmids • decrease membrane permeability to ABX • decrease affinity of PCN binding protein • increase concentration of binding proteins

  47. ABX Resistance Hochberg, Rheumatology, 4th edition

  48. MMWR, April 25, 2008 / 57(16);435 • Cefixime 400mg PO BID • Lupin Pharmaceuticals, Inc. (Baltimore, Maryland, 866-587-4617).

  49. Summary • Gonorrhea remains most common communicable disease in US • DGI is most common acute septic arthritis in young adults in US • DGI is spectrum of disease • Definite diagnosis challenging • Culture from all mucosal sites • Treatment challenge due to resistance

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