Clinical Approach to Acute Monoarthritis Mohammad Hasan Jokar

Acute Arthritis The sudden onset of inflammation of the joint, causing severe pain, swelling, and redness. Structural changes in the joint itself may result from persistence of this condition.

Signs of Inflammation Swelling Warmth Erythema Tenderness Loss of function

Key Points Distinguish arthritis from soft tissue non articular syndromes (discrepancy between “active” and “passive” ROM suggests periarticular/soft tissue) If the problem is articular distinguish single joint from multiple joint involvement Inflammatory or non-inflammatory disease Always consider septic arthritis!

Articular Vs. Periarticular Clinical feature Articular Periarticular Anatomic structure Painful site Pain on movement Swelling Synovium, cartilage, capsule Diffuse, deep Active/passive, all planes Common Tendon, bursa, ligament, muscle, bone Focal “point” Active, in few planes Uncommon

Inflammatory Vs. Noninflammatory Feature Inflammatory Noninflammatory Pain (when?) Swelling Erythema Warmth AM stiffness Systemic features î ESR, CRP Synovial fluid WBC Examples Yes (AM) Soft tissue Sometimes Prominent Frequent WBC >2000 Septic, RA, SLE, Gout Yes (PM) Bony Absent Minor (< 30 ‘) Uncommon WBC < 2000 OA, AVN

Acute Monoarthritis Inflammation (swelling, tenderness, warmth) in one joint Occasionally polyarticular diseases can present with monoarticular onset: (RA, JRA,Reactive and enteropathic arthritis, Sarcoid arthritis, Viral arthritis, Psoriatic arthritis)

Acute Monoarthritis - Etiology THE MOST CRITICAL DIAGNOSIS TO CONSIDER: INFECTION ! Septic Crystal deposition (gout, pseudogout) Traumatic (fracture, internal derangement) Other (hemarthrosis, osteonecrosis, presentation of polyarticular disorders)

Questions to Ask – History Helps in DD Pain come suddenly, minutes? – fracture. 0ver several hours or 1-2 days? –infectious, crystals, inflammatory arthropathy. History of IV drug abuse or a recent infection? – septic joint. Previous similar attacks? – crystals or inflammatory arthritis. Prolonged courses of steroids? – infection or osteonecrosis of the bone.

Acute Monoarthritis

Indications for Arthrocentesis The single most useful diagnostic study in initial evaluation of monoarthritis: SYNOVIAL FLUID ANALYSIS 1. Suspicion of infection 2. Suspicion of crystal-induced arthritis 3. Suspicion of hemarthrosis 4. Differentiating inflammatory from noninflammatory arthritis

Tests to Perform on Synovial Fluid Total leukocyte count/differential: inflammatory vs. non-inflammatory. Polarized microscopy to look for crystals. Gram stain and cultures Not necessary routinely: Chemistry (glucose, total protein, LDH) unlikely to yield helpful information beyond the previous tests.

Case 1 52 yo wm presents to the Emergency Department with a 2 day history of excrutiating pain, with swelling, of the left knee. He denies a history of trauma. He reports fever of 39 degrees and chills.

Physical Exam: T= 39.5 BP=150/92 P=105 RR=18 The physical exam is notable only for the musculoskeletal exam which reveals: Left knee with erythema, warmth, and swelling. There is exquisite tenderness and pain with any motion. There is reduced range of motion due to pain. Other joints are normal.

The presentation of monoarticular arthritis *****Aspiration of the joint*****

Lab tests CBC Joint fluid study Blood culture

Synovial fluid WBC 92,000 97 % PMNs Gram Stain

Septic Arthritis Key Features: Monoarticular (almost always) Dolor, rubor, calor Swelling Exquisite pain Synovial fluid >50K WBCs and >95% PMNs Aggressive disease warranting aggressive management

Septic Arthritis Management of the patient with septic arthritis Arthrocentesis Hospital admission Orthopedic consult IV antibiotics Broad spectrum antibiotics until culture and sensitivity available

Septic arthritis ******Drainage of the pus****** ******IV antibiotics are essential******

Septic Arthritis Staphylococcus aureus - most aggressive Rapid evolution to joint destruction Importance of rapid diagnostic studies Rapid initiation of therapy Surgical drainage Intravenous antibiotics

Epidemiology 1:1 M:F Mean Age=55 85%=Monoarticular Patients with Damaged Joints are at Increased Risk Most are hematogenously spread Fever present in only 60% of non-GC septic arthritis Crystalline arthritis is 4x as common as septic arthritis; fevers/rigors non-specific Direct penetration into a foot joint through a sneaker is usually Pseudomonas.

Specific Infectious Agents Causative agents identified in 2/3 of patients in whom suspected 50% have known portal of entry 25% are iatrogenic 75% have extra-articular source: Look for skin, respiratory, or GU sources

Groups at risk for septic arthritis Rheumatoid Arthritis: Account for up to 50% of cases Immunosuppressed Host, especially Organ Transplant Patients Advanced Age: Greater than 60, especially with Prosthetic Joints: May result in Osteomyelitis Diabetes Neoplasm IV Drug Use: Repetitive transitory Bacteremia: Staphylococci (MRSA)>Enterobacter, Serratia, and Pseudomonas Hemodialysis: Recurrent Vascular Infections, especially Staphylococci RA: Poor clearance of bacteria from synovial fluid, phagocytic defects due to drugs or disease, long-standing, severe RA. Reported mortality: 15 to 22% when monoarticular, up to 44% when polyarticular. Prosthetic Joints: Pain>>Effusion. Fever and Hi WBC often absent, ESR may be normal, although often elevated. S. epi=40% of both early and late infections. 3-phase bone scans are surprisingly insensitive. Value of gram stain is questionable. Knee replacement can be repeated as a 2 step procedure: total debridement followed by 4 to 6 weeks of antibiotics. Cefotaxime or Inepenem or Fluoroquinolone

Right wrist destruction by Staphylococcus aureus

Antibiotics and Supportive Therapy Guided by local antibiotic sensitivity patterns Intra-articular antibiotics are not required and may cause a chemical synovitis Usually administered for 4 to 6 weeks NSAID’s avoided until the diagnosis is secure Joint Immobilization for 1 to 3 days ROM as soon as possible

Case 2 22 yo wf presents to the Emergency Department with c/o left wrist pain of 2 days’ duration. She reports 2 weeks ago, the onset of left ankle pain and swelling which subsequently resolved in 3 days. She then developed 3 days of swelling and pain in the left knee, followed by 3 days of swelling and pain in the right knee.

Physical Exam Temp 39 Normal examination of HEENT, Lungs, CV, and Abdomen Skin: Pustular lesions right 3rd and 4th fingers Musculoskeletal: Left wrist warm, swollen (arthritis) with erythema extending along the extensor tendons of the hand (tenosynovitis)

Gonorrhea: rash, vesicle, and pustule Early lesions of gonococcemia are shown on the hand of a young patient with gonococcal arthritis. Single small vesicles or pustules are common. The lesion on the left is a hemorrhagic vesicle and that on the right is a pustule. Gonococcal lesions are typically few in number and located on the extremities. #9118010

Gonorrhea: rash, pustule, and bulla The rash of disseminated gonococcal infection can occur on any exposed portion of the skin. Since there are usually few gonococcal skin lesions, they must be specifically sought since they can be easily missed on cursory examination. The triad of arthritis, cutaneous lesions (vesicopustules and hemorrhagic lesions), and fever may also be seen in meningococcemia as well as in gonococcemia. Culture of these lesions may be positive for the inciting organism. Left, A pustule with a necrotic center is surrounded by inflammation. Right, A large hemorrhagic blister (bulla), a less common cutaneous lesion, is shown. #9118020

Gonorrhea: pustule Gonorrhea: pustule A pustule surrounded by erythema proximal to the first metacarpophalangeal joint is present in a patient with disseminated gonococcemia. These lesions, typically few in number, are usually located on the extremities. #9118030

Gonococcal Arthritis Key Features Migratory arthritis (immune mediated or reactive) Tenosynovitis Rash Sexually active patient (though this may not be disclosed on history)

Gonococcal Arthritis Evaluation Aspiration of affected joint Culture Inflammatory joint fluid (>2000 WBC’s) Rarely WBC count in the “septic” range (>50,000 WBC’s) Cultures usually negative Culture Oropharynx, anus, cervix/urethra, skin lesions

Gonococcal Arthritis Migratory Polyarthralgias/Polyarthritis/Tenosynovitis = 66%; Knee>hand>wrist Dermatitis=sparse peripheral necrotic pustules in 40% 83%=female, mean age=23, GU involvement in 63%, often asymptomatic Check VDRL and HIV and Co-treat Chlamydia DGI-like arthritis-dermatitis can also occur with H. influenzae, N. meningitidis, and S. moniliformis Is GC arthritis still sensitive to Penicillin? DGI=Disseminated Gonococcal Infection=Arthritis, tenosynovitis, and dermatitis Frequency of + Cultures: GU 86%, joint fluid 44%, rectal 39%, blood 39%, pharyngeal 7% Fluoroquinolone resistance is now rarely reported. Female genital infection may have occurred long before systemic dissemination. Negative joint cultures may reflect sterile inflammation induced by immune complexes. If recurrent Neisseria infections, look for terminal complement deficiencies.

Management Antibiotics Ceftriaxone Doxycycline added (to cover likely concomittant Chlamydia infection) Surgical drainage of the joint rarely necessary

Case3 32 y/o WM admitted to the hospital with 2 days of acute onset of arthritis in his right knee that progressed to the left knee. The day previous to the admission, he was evaluated in the ER, and an arthrocenthesis was attempted. The patient was discharged on ceohalexin 500 mg QID. ROS: 3 weeks previous to admission he had an episode of diarrhea that lasted for 10 days and improved after treatment with Cipro. Family History: Sister with recurrent uveitis.

Physical Examination PE: fever 38.5. Otherwise within normal limits. Joint exam: tenderness, redness and effusions in both knees. Labs: ESR 60, Synovial fluid showed no crystals and Gram stain revealed no organisms. HLA B-27 positive. Patient was started on indomethacin 50 mg PO QID with significant improvement of his symptoms.

Reactive Arthritis “Reactive Arthritis (ReA) is an infectious induced systemic illness characterized by an aseptic inflammatory joint involvement occurring in a genetically predisposed patient with a bacterial infection localized in a distant organ/system”.

Reactive Arthritis Epidemiology ReA is an acute and insidious polyarthritis after an enteric and urogenital infections. Incidence varies widely (1% to 20%). Frequency varies from 0 to 15% after infection with Salmonella, Shigella, Campylobacter or Yersinia. HLA-B27 can be present in 72% to 84% of the cases. Incidence after Chlamydia trachomatis is not well known.

Reactive Arthritis ReA can occurs in the absence of HLA-B27, this play a very important role.

Reactive Arthritis Causative organisms Frequent association: Chlamydial trachomatis Ureaplasma urealyticum Salmonella enteritidis Salmonella typhimurium Shigella flexneri Shigella dysenteriae Campylobacter jejuni Yersinia enterocolitica Streptococcus SP

Reactive Arthritis Less common association: Chlamydia pneumoniae Neisseria meningitidis serogroup B Bacillus cereus Pseudomonas Clostridium difficile Borrelia burgdorferi Escherichia coli Helicobacter pillory Lactobacillus Brucella abortus Hafnia alvei

Reactive Arthritis Clinical Manifestations: Postenteric ReA is described equally in men an women. Postchlamydial is most common in men. In patients with postenteric ReA, the episode of diarrhea is usually prolonged. Arthritis presents usually 2 to 3 weeks after the episode of diarrhea. Arthritis usually resolves within 6 months, but a few patients had recurrences an a minority develops a chronic arthritis.

Reactive Arthritis In patients with postchlamydial disease, urethritis is usually mild, painless and nonpurulent. Conjunctivitis is usually observed very early, before the onset of arthritis, uveitis is less common but occurs in 15% of patients with chronic persistent disease. Skin manifestations include: Keratoderma blenorrhagica, Circinate balanitis and oral ulcers. Less common patients can develop valvulitis, rhythm disturbances.

Reactive Arthritis Treatment: NSAIDS are the first line of treatment. In patient with frequent recurrences or chronic arthritis benefit from DMARDS such us sulfasalazine or methotrexate. If there is axial involvement they will benefit from TNF-alpha blockers. Topical steroids are indicated in conjunctivitis and uveitis. In monoarthritis steroid injections could be beneficial.

Case 4 24 yo wm treated for gonococcal urethritis 2 weeks prior to presentation has complaint of low back pain, left ankle and right knee pain and swelling. He has noted “pink eye” in his left eye.

Physical exam Afebrile HEENT- Left eye with conjunctival injection Musculoskeletal- Tender right SI joint Effusion with warmth and tenderness of left ankle and right knee

Evaluation CBC, CMP- normal ESR- 62 U/A- neg protein, 2 WBCs, 5 RBCs Culture and sensitivity negative Xrays- SI joints, knees, ankles- normal

Reiter’s Syndrome (Reactive Arthritis) Triad: Conjunctivitis, urethritis, arthritis Other features: Sausage digits, oral erosions, keratoderma blenorrhagicum, circinate balanitis Triggered by a recent GI/GU(STD) infection

Keratoderma Blennorrhagicum

Reiter’s Syndrome Key Features: Preceding GI/GU infection The GU infection may have been asymptomatic (especially in women), or not yet detected Triad: Conjunctivitis, urethritis, arthritis (lower extremity>upper, asymmetric, oligoarticular) Usually self-limited (3-12 month course) 15% develop chronic, destructive arthritis

Reiter’s Syndrome Radiographic features Xrays may be normal acutely, however changes develop over time Periostitis Sacroiliitis Unilateral

Reiter’s Syndrome Management Detection of underlying infection Treatment of underlying infection NSAID’s DMARD’s- mixed results Best evidence supports use of sulfasalazine

Case 5 45 yo m presents to the Emergency Department with a 12 h history of excrutiating pain, with swelling, of the left foot

Physical Exam: T= 39 BP=150/92 P=105 RR=18 The physical exam is notable only for the musculoskeletal exam which reveals: Left foot with erythema, warmth, and swelling. There is exquisite tenderness and pain with any motion. There is reduced range of motion due to pain. Other joints are normal.

Lab tests CBC: WBC 13000 PMN 85% Creatinine:1 Uric acid :6.5 Synovial fluid :40000 90% PMNs

Management of gouty arthritis Asymptomatic hyperuricemia Acute gouty arthritis Chronic or tophaceous gout

Purine nucleotides Xanthine oxidase hypoxanthine xanthine Uric acid Urinary excretion Alimentary excretion Tissue deposition in excess Urate crystal microtophi Phagocytosis with acute inflammation and arthritis

Management of gouty arthritis Asymptomatic hyperuricemia Acute gouty arthritis Chronic or tophaceous gout

Management of gouty arthritis Treatment of asymptomatic hyperuricemia usually in not necessary

Preventive measures Avoiding excess weight gain Reducing risks for hypertension Avoiding diuretic therapy Control alcohol intake

Management of gouty arthritis Asymptomatic hyperuricemia Acute gouty arthritis Chronic or tophaceous gout

Purine nucleotides hypoxanthine Xanthine oxidase xanthine Uric acid Urinary excretion Alimentary excretion Tissue deposition in excess Urate crystal microtophi Phagocytosis with acute inflammation and arthritis colchicine NSAID

Management of acute gout Do not attempt to modify plasma urate concentrations NSAID Colchicine steroids

Management of acute gout NSAID Shorter half life Indomethacin (50mg qid-50mg tid-25mg tid) Ibuprofen 800mg q6h Contraindications Renal insufficiency, peptic ulcer, warfarin therapy, liver disease, chronic heart failure

Management of acute gout Colchicine Effective within the 24 hours of an attack Mechanism of colchicine Inhibit phagocytosis (microtubular system) Affect chemotaxis Affect motility and adhesion of neutrophil Reduce release PGE2 and LTB4

Management of acute gout Colchicine Side effect GI disturbance, blood dyscrasias, myoneuropathy Contraindications Renal dysfunction, liver disease, sepsis, bone marrow dysfunction

Management of acute gout Corticosteroids NSAID and colchicine are contraindicated Prednisone 20-50mg oral 3-20days Intra-articular steroids

Prophylactic therapy Indications Recurrent attacks Tophi Renal disease Uric acid urolithiasis Inherited metabolic disorders Degree of hyperuricemia (11.8 mg/dl)

Prophylactic therapy Colchicine NSAID Urate-lowering therapy Allopurinol Uricosuric agents Induce a flare up Concurrent colchicine prophylaxis

Purine nucleotides hypoxanthine allopurinol Xanthine oxidase xanthine Uric acid Urinary excretion Alimentary excretion Tissue deposition in excess Urate crystal microtophi uricosurics Phagocytosis with acute inflammation and arthritis colchicine NSAID

Prophylactic therapy Dietary restriction of purines rarely causes a fall in the plasma urate concentration more than 1.0 gm/dl Flares occure during a fall in serum urate level

Purine nucleotides hypoxanthine allopurinol Xanthine oxidase xanthine Uric acid Urinary excretion Alimentary excretion Tissue deposition in excess Urate crystal microtophi Phagocytosis with acute inflammation and arthritis

Prophylactic therapy Allopurinol Indications Xanthine oxidase inhibitor Indications Renal insufficiency Nephrolithiasis Tophi Tumor lysis syndrome Primary metabolic defects

Prophylactic therapy Allopurinol 300mg-900mg Side effect (<2%) Potentiating imuran marrow suppressive effect Hypersensitivity syndrome Hepatitis Interstitial nephritis

Purine nucleotides hypoxanthine Xanthine oxidase xanthine Uric acid Urinary excretion Alimentary excretion Tissue deposition in excess Urate crystal microtophi uricosurics Phagocytosis with acute inflammation and arthritis

Prophylactic therapy Uricosuric agents Mechanism Probenecid Sulphinpyrazone Benzbromarone Mechanism Inhibit renal tubular reabsorption

Prophylactic therapy Uricosuric agents Side effects Contraindications Uric acid crystalluria GI disturbance Allergy Hepatic impairment Contraindications Renal insufficiency nephrolithiasis

Prophylactic therapy When instituting uricosuric therapy Concurrent colchicine prophylaxis Initial low dose, increase dose gradually Maintain alkaline diuresis Not use in urine volume less than 1400ml/24 hours

Purine nucleotides hypoxanthine allopurinol Xanthine oxidase xanthine Uric acid Urinary excretion Alimentary excretion Tissue deposition in excess Urate crystal microtophi uricosurics Phagocytosis with acute inflammation and arthritis colchicine NSAID