1. Mendoza, T., Mindanao, A., Miranda, M., Molina, M., Monzon, J., Morales, A., Musni, M., Nallas, A., Naval, A., Nepomuceno, J., Nerpiol, C., Ng, C., Ng, P., Niere, J., Millicent Tan Ong, MD Helmar Soldevilla, MD 3C-MED Medicine II –Module 4 Clinical Case: Psoriasis Psoriatic Arthritis Cellulitis 1

2. OBJECTIVES To present a case of a 28 y/o male with Psoriatic Arthritis (PsA) Differential Diagnoses Psoriatic Arthritis –Epidemiology –Pathophysiology –Clinical Features Approach to a Patient with PsA Complications, Outcome and Prognosis of PsA 2

3. MEDICAL HISTORY 28 year old male, catholic, married, tricycle driver, residing in Caloocan City Chief Complaint: 3

4. History of Present Illness 7 Yrs PTA Diagnosed with Psoriasis based on the following: Flaky white scales on the scalp Pustules, papules  plaques topped with scales at the back, trunk, upper and lower extremities and his face Punch biopsy: Psoriasis Rx: Psoralen + Ultraviolet A (PUVA) therapy Methotrexate (2.5mg) at 12 hr intervals for three doses each week Dermovate (unrecalled dose) with Petroleum Jelly and LCD Hydroxizine (Iterax) for pruritus 3x/day prn Full resolution of skin lesions Diagnosed with Psoriasis based on the following: Flaky white scales on the scalp Pustules, papules  plaques topped with scales at the back, trunk, upper and lower extremities and his face Punch biopsy: Psoriasis Rx: Psoralen + Ultraviolet A (PUVA) therapy Methotrexate (2.5mg) at 12 hr intervals for three doses each week Dermovate (unrecalled dose) with Petroleum Jelly and LCD Hydroxizine (Iterax) for pruritus 3x/day prn Full resolution of skin lesions 2 Yrs PTA Recurrence of skin lesions Pain and swelling of all the digits of both hands Rx: Naproxen (550mg/tab) BID prn Asymmetric oligoarthritis  polyarthritis involving the DIPs and PIPs of both hands, BKJ Consult to Rheumatologist Rx: Celecoxib (unrecalled dose) Recurrence of skin lesions Pain and swelling of all the digits of both hands Rx: Naproxen (550mg/tab) BID prn Asymmetric oligoarthritis  polyarthritis involving the DIPs and PIPs of both hands, BKJ Consult to Rheumatologist Rx: Celecoxib (unrecalled dose) 4

5. 1 month PTA persistent swelling on BKJ with↑ pain (VAS 9/10) 1 week PTA Non-radiating pain (VAS 7/10) on the low back, hips, and BAJ More difficulty in ambulation Non-radiating pain (VAS 7/10) on the low back, hips, and BAJ More difficulty in ambulation 5 days PTA Consult to Orthopedic Surgeon; diagnosed with BKJ effusion & advised arthrocentesis 4 days PTA Undocumented fever temporarily relieved by Cefuroxime and Paracetamol (unrecalled dose) Consult at FEU Hospital: (X-Ray of leg: soft tissue swelling) Advised admission but refused due to financial constraints Transferred to USTH for further evaluation & management Undocumented fever temporarily relieved by Cefuroxime and Paracetamol (unrecalled dose) Consult at FEU Hospital: (X-Ray of leg: soft tissue swelling) Advised admission but refused due to financial constraints Transferred to USTH for further evaluation & management ADMISSION 1 Yr PTA Pain and swelling on both knee joints (BKJ)  limping Relieved by various unrecalled NSAIDs Pain and swelling on both knee joints (BKJ)  limping Relieved by various unrecalled NSAIDs 5

6. Past Medical History (-) DM (-) HPN (-) Joint surgery (-) history of trauma (-) Allergy Diagnosed with dengue fever (2 nd year high school) Excision of cyst at the back (2007) 6

7. Family History (+) Myocardial Infarction – father (+) DM – father (-) HPN (-) stroke (-) Psoriasis (-) Cancer (-) Arthritides 7

8. Personal & Social History Smoker: 0.6 pack years Occasional Alcoholic Beverage Drinker Denies Illicit Drug Use 3 past sexual partners, all protected Tricycle driver No history of travel outside manila 8

9. Review of Systems No wt. loss, no loss of appetite No hearing loss, no nasal congestion, no cough No dyspnea, orthopnea, cyanosis No chest pain, palpitations No abdominal pain, diarrhea, constipation No dysuria, frequency, change in character of urine 9

10. PHYSICAL EXAMINATION General Survey Conscious, coherent, oriented as to time, place and person, not in cardio-respiratory distress Vital Signs BP 120/70 mmHg Wt: 70 kgs PR 83 bpm Ht: 1.62 m RR 20 cpm BMI : 26.5 kg/m 2 T° = 36.6 °C Skin (+) generalized erythema w/ multiple well- to ill-defined papules and plaques topped with whitish scales over the scalp, trunk and extremities (+) onychodystrophy, nail pitting, oil spots of all nails of the hands and feet 10

11. HEENT Pink palpebral conjunctivae, anicteric sclerae, no naso- aural discharge, no tragal tenderness, moist buccal mucosa, nonhyperemic PPW, tonsils not enlarged Neck Supple neck, trachea midline, no palpable cervical lymph nodes, thyroid gland not enlarged Cardiovascular Adynamic precordium, AB at 5 th LICS, MCL; no murmurs All pulses full and equal Respiratory Symmetric chest expansion, no retractions, clear breath sounds on all lung fields, no crackles, no wheezes Abdomen Flat abdomen, NABS, soft, nontender, no masses 11

12. Musculoskeletal Hand (+) sausage-shaped 2 nd and 4 th digit of the right hand & 4 th & 5 th digits of the (L) hand (+) Flexion contracture of the DIPs of the 2 nd, 4 th and 5 th digits of the (R) hand & 5 th digit of the (L) hand (+) tender, swollen, erythematous DIPs and PIPs of the 2 nd, 4 th and 5 th digits of the ® hand and DIP of the 4 th and 5 th digit of the (L) hand All Active Range of Motion (AROM) of bilateral hands are within normal limits EXCEPT: (L) hand (R) hand (R )DIPPIP 2 nd digit45-45°0-30° 4 th digit45-45°0-45° 5 th digit30-30°0-50° Passive Range of Motion (PROM) not assessed due to tenderness of the affected joints (L)DIPPIP 4 th digit0-45° 5 th digit50-50°0-40° 12

13. Landmark: Medial Tibial Plateau RIGHTLEFTDIFFERENCE 3 inches40.5 cm38 cm2.5 cm 6 inches40.5 cm37.5 cm3 cm 9 inches30.5 cm28 cm2.5 cm BKJ (+) swelling, warmth, tenderness PROM within normal limits Legs swollen, warm, tender, erythematous (R) leg Limb Girth Measurement AROM(R)(L) BKJ0-100°0-125° 13

14. SALIENT FEATURES 28 y/o male History of Psoriasis Asymmetric oligoarthritis  polyarthritis of the affected DIPs and PIPs of both hands, BKJ, and (BAJ) (+) Flexion contracture of the DIPs of the affected digits (+) sausage-shaped digits Limited AROM of the affected joints BKJ effusion swollen, warm, tender, erythematous (R) leg Undocumented fever Pertinent (+) 14

15. SALIENT FEATURES No history of morning stiffness of joints No hx of bacterial infection or serious chronic illness No hx of infection before onset of arthritis No family history of arthritides Pertinent (-) 15

16. Upon admission: Arthrocentesis Aspirated knee: 42cc (R) knee, 18cc (L) Gram stain = no microorganisms 1 st hospital day Cefazolin 1g/IV every 8 hours Dolcet tablet (pain) Paracetamol (temperature exceeding 38.0 ⁰ C) 2 nd hospital day Dermatology; advised to continue using Dove Extrasensitive Soap and Petroleum Jelly Advised to have regular leg exercises (improve mobility) Noted to have febrile episodes and tender, warm swelling of (R) leg Medications still continued 4 th hospital day, decrease swelling of (R) leg, afebrile 6 th hospital day, started on Cloxacillin 500mg/cap, 1 capsule every 6 hours Course in the Ward 16

17. OBJECTIVES To present a case of a 28 y/o male with Psoriatic Arthritis (PsA) Differential Diagnoses Psoriatic Arthritis –Epidemiology –Pathophysiology –Clinical Features Approach to a Patient with PsA Complications, Outcome and Prognosis of PsA 17

18. 3C-MED DIFFERENTIAL DIAGNOSES 18

19. MUSCULOSKELETAL COMPLAINT TENDONITIS BURSITIS MYOFASCIAL PAIN INFLAMMATION PRESENT: MONOARTHRITIS PAUCIARTHRITIS POLYARTHRITIS HISTORY & PE NONARTICULAR ARTICULAR MINIMAL: OSTEOARTHRITIS 19

20. INFLAMMATORY ARTICULAR MONOARTHRITISPAUCIARTHRITISPOLYARTHRITIS PROMINENT SPINE INVOLVEMENT: Ankylosing Spondylitis Psoriatic arthritis MINIMAL SPINE INVOLVEMENT: Rheumatoid arthritis SLE Gout Septic Arthritis 20

21. Harrison’s Principles of Internal Medicine 17 th edition 21

22. PSORIATIC ARTHRITIS SEPTIC ARTHRITIS REACTIVE ARTHRITIS GOUTRHEUMATOID ARTHRITIS NatureInflammatory Arthritis InfectiousAcute nonpurulent arthritis Metabolic DiseaseAutoimmune Disease Process Inflamed synovium with less hyperplasia and cellularity than in RA Direct invasion of joint space by various microorganisms, including bacteria, viruses, mycobacteria, and fungi Acute, nonpurulent arthritis occurs after infection Inflammatory reaction to microcrystal of sodium urate Chronic inflammation of synovial membranes w/ secondary erosion of adjacent cartilage and bone Cause genetic and environmental factors, immune- mediated Bacterial Infection (Gnococcal, Nongonococcal), Fungi, Virus Shigella (S. flexneri), Salmonella, Yersinia, Deposition of MSU in joint and connective tissue tophi Unknown Sex M = WM > FEnteric: M = W Venereal: M > W M > F M = F postmenopausal F 3X > M Age20-30- y/o 50-60 y/o > 65 y/o18 – 40 y/oMiddle age to elderly men and post menopausal women 4th – 5th decade of life Clinical Presentation Oligoarthritis, PolyArthritis, Axial Arthritis Subacute or Chronic monoarthritis, Acute Polyarticular Isolated transient monoarthritis Acute ArthritisChronic Polyarthritis SymmetryAsymmetric/ Symmetric Asymmetric Viral - Symmetric AsymmetricSymmetric 22

23. PSORIATIC ARTHRITIS SEPTIC ARTHRITIS REACTIVE ARTHRITIS GOUTRHEUMATOID ARTHRITIS No. of jointsOligoarticular / Polyarticular Monoarticular or Polyarticular MonoarticularMono / oligoarticular Initially : mono Subsequent: poly Polyarticular Most common joint affected DIPKnee, Hip, Shoulder, Ankle, Wrists Joints of lower extremities (Knee, Ankle) MTP joint of big toePIP and MCP joints Progression and Duration Erosive disease develops, progressive disease w/ deformity and disability Acute, additive w/ involvement of new joints in a few days to 1-2 weeks Occasionally isolated attacks lasting days up to 2 weeks Often chronic with remissions and exacerbations SwellingDactylitis (>30%), Enthesitis, Tenosynovitis PresentDiffuse swelling of a solitary finger or toe, Dactylitis or sausage-finger, Tenidinitis and fasciitis Present within and around the involved joint Synovial tissue in joints or tendon sheaths StiffnessMorning stiffnessProminent, often for an hour or more in the morning, also after inactivity Limitations of motion reduced range of motion marked limitation of both active and passive ranges of motion Patient cannot walk without support Motion is limited primarily by pain Motion limited by pain 23

24. PSORIATIC ARTHRITIS SEPTIC ARTHRITIS REACTIVE ARTHRITIS GOUTRHEUMATOID ARTHRITIS Generalized Symptoms Silver or grey scaly spots on the scalp, elbows, knees etc, Lifting or pitting of fingernails/toenails Redness and pain in the eye Fever, arthralgias of multiple joints, and multiple skin lesions Fatigue, malaise, fever and weight loss Fever may be present Weakness, fatigue, weight loss, and low fever are common, lymphadenopathy and splenomegaly Radiologic featureClassic pencil-cup deformity, marginal erosions w/ adjacent bony proliferation (whiskering), small- joint ankylosis, osteolysis of phalangeal and matecarpal bone, periostitis Soft-tissue swelling, joint- space widening, displacement of tissue planes by distended capsule Absent or confined to juxtaarticular osteoporosis, marginal erosions and loss of joint space, Periostitis w. reactive new bone formation, spurs at the inseertion of plantar fascia Cystic changes well defined erosion with sclerotic margins (often overhanging bony edges) Soft tissue masses characterized radio features of advanced chronic tophaceous gout Soft tissue swelling and joint effusion Juxta articular osteopenia loss of articular cartilage Bone erosion Associated deformities Pencil-cup deformity Telescoping of fingers/ Opera- glass deformity Heberden’s node Bouchard’s node Swan node deformity, Boutonniere deformity, Baker’s cyst Extraarticular Manifestations Psoriatic skin lesions Conjunctivitis Urogenital lesions Conjunctivitis Keratoderma blenorrhagica Circinate Balanitis Uric acids nephrolithiasis Rheumatoid nodules Rheumatoid vasculitis Pleuropulmonary manifestations Caplan’s & Felty’s syndrome Osteoporosis 24

25. 3C-MED CLINICAL IMPRESSION: PSORIATIC ARTHRITIS 25

26. An inflammatory arthritis that characteristically occurs in a patient with psoriasis. Harrison’s Internal Medicine 17 th edition A form of arthritis that occurs in patients with psoriasis with the hallmarks of an "inflammatory" arthritis, including joint pain, erythema, and swelling, often with prominent stiffness. Mease, P., Menter, A. (2005), Psoriatic Arthritis: Understanding Its Pathophysiology and Improving Its Diagnosis and Management. Retrieved from: http://cme.medscape.com/viewarticle/509053 26

27. OBJECTIVES To present a case of a 28 y/o male with Psoriatic Arthritis (PsA) Differential Diagnoses Psoriatic Arthritis –Epidemiology –Pathophysiology –Clinical Features Approach to a Patient with PsA Complications, Outcome and Prognosis of PsA 27

28. EPIDEMIOLOGY 5-30% prevalence of PsA among individuals with psoriasis 60 – 70% psoriasis precedes joint disease 15 – 20% psoriasis and PsA appear within 1 yr of each other 15-20%arthritis precedes the onset of psoriasis M = F 2 peaks in onset: –20 – 30 y/o –50 – 60 y/o Harrison’s Principles of Internal Medicine 17 th edition Feldman, Pearce, Epidemiology, Clinical manifestations, and Diagnosis of Psoriasis; May 13, 2009 28

29. 3C-MED PATHOPHYSIOLOGY 29

30. VIDEO HYPERLINK Psoriasis 30

31. 31

32. 32

33. 3C-MED CLINICAL FEATURES 33

34. CLINICAL FEATURES pain and stiffness in the affected joints –morning stiffness lasting more than 30 minutes –stiffness accentuated with prolonged immobility –alleviated by physical activity On PE : –stress pain – joint line tenderness –effusions in the affected joints asymmetric distribution The distal interphalangeal joints and spine affected in 40 to 50 % percent of cases Gladman,D. (2008), Clinical Manifestations of Psoriatic Arthritis, 34

35. Clinical Features Unique to Psoriatic Arthritis: –DIP joint involvementDIP joint involvement –Nail changesNail changes –DactylitisDactylitis –Enthesitis –Spondylitis Lytic and periarticular new bone formation x-ray features –Iritis or Uveatis Mease, P., Menter, A. (2005), Psoriatic Arthritis: Understanding Its Pathophysiology and Improving Its Diagnosis and Management. Retrieved from: http://cme.medscape.com/viewarticle/509053 35

36. CLINICAL FEATURES SCHEME OF WRIGHT AND MOLL –ARTHRITIS OF DIP JOINTS –ASYMMETRIC OLIGOARTHRITIS –SYMMETRIC POLYARTHRITIS –AXIAL INVOLVEMENT –ARTHRITIS MUTILANS OLIGOARTHRITIS POLYARTHRITIS AXIAL ARTHRITIS Harrison’s Principles of Internal Medicine 17 th edition 36

37. Psoriatic Arthritis Distal Interphalangeal joint arthritis Occurs in 15 % of cases Nail changes also seen Harrison’s Internal Medicine 17 th edition 37

38. Psoriatic Arthritis Asymmetric Oligoarthritis Involves the knee or any large joint with a few small joints in the fingers and toes –Metarsophalangeal –Proximal interphalengeal –Distal interphalengeal Dactylis –Sausage shaped digits due to inflammation of the flexor tendons and synovium and pitting edema of the distal extremities may be observed Harrison’s Internal Medicine 17 th edition 38

39. Psoriatic Arthritis Symmetric polyarthritis Affects the Hands, wrists, knees, and feet symmetrically –Proximal interphalangeal joints –Metacarpophalangeal joints Peripheral joints are less tender compared to RA Harrison’s Internal Medicine 17 th edition 39

40. Psoriatic Arthritis Axial Arthropathy Spine and sacroiliac joints Harrison’s Internal Medicine 17 th edition 40

41. Psoriatic Arthritis Arthritis mutilans Widespread shortening or telescoping of digits due to osteolysis of the phalanges and metacarpals coexisting with ankylosis and contractures in other digits opera-glass deformity or pencil-in-cup radiographic findings Fever Harrison’s Internal Medicine 17 th edition 41

42. CLINICAL FEATURES Articular features: DACTYLITIS ENTHESITIS TENOSYNOVITIS “TELESCOPING”/SHORTENING OF DIGITS BACK AND NECK PAIN AND STIFFNESS NAIL CHANGES: –PITTING, HORIZONTAL RIDGING, ONYCHOLYSIS, YELLOWISH DISCOLORATION OF NAIL MARGINS, DYSTROPHIC HYPERKERATOSIS, COMBINATION 42

43. Nail Changes Pitting Horizontal ridging Onycholysis Discoloration of nail margins Dystrophic hyperkeratosis Onycholysis Nail pitting Onychodystrophy Harrison’s Internal Medicine 17 th edition 43

44. Dactylitis Involvement of the distal and proximal interphalangeal joints, together with tendon sheath involvement, may give the digit a sausage shape Enthesitis Inflammation at the sites of ligamentous and tendinous insertions Harrison’s Internal Medicine 17 th edition 44

45. The Classification Criteria for Psoriatic Arthritis (CASPAR) Presence of musculoskeletal inflammation (an inflammatory arthritis, enthesitis, or back pain); PLUS any three of the following: Skin psoriasis (present, previously present by history, or a family history of psoriasis if the patient is not affected) Nail lesions (onycholysis, pitting, and hyperkeratosis ) Dactylitis (present or past) Negative rheumatoid factor Juxtaarticular bone formation on radiographs These criteria have now been tested in psoriatic arthritis and were both sensitive (91.4%) and specific (98.7 %) Taylor W, Gladman D, Helliwell P, etal. CASPAR Study Group. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006 Aug;54(8):2665- 73. 45

46. OBJECTIVES To present a case of a 28 y/o male with Psoriatic Arthritis (PsA) Differential Diagnoses Psoriatic Arthritis –Epidemiology –Pathophysiology –Clinical Features Approach to a Patient with PsA Complications, Outcome and Prognosis of PsA 46

47. 3C-MED DIAGNOSTIC WORK-UPS 47

48. NO diagnostic laboratory tests ↑ESR and ↑ CRP Extensive psoriasis = uric acid may be elevated Check for gout Test for HLA-B27 48

49. Reference8/27/09 Hgb120-170 d/L105 Hct0.37-0.540.32 RBC4-6x 10^12/L4.03 WBC4.5-10x 10^9/L8.60 Neutrophil0.50-0.700.70 Segs0.50-0.700.70 Bands Lympho0.20-0.400.30 Mono0-0.07 Eos0-0.05 Plt150-450x 10^9/L552 MCV87 +/-5 U^379.60 MCH29+/-2 pg26.0 MCHC34+/-2 g/dL32.70 RDW25.9013.40 Reference8/27/09 Hgb120-170 d/L105 Hct0.37-0.540.32 Plt150-450x 10^9/L552 MCV87 +/-5 U^379.60 RDW25.9013.40 49

50. Reference8/27/09 BUN9-236.9 Crea0.5-0.20.76 AST-SGOT0-3227.3 ALT-SGPT0-3141.2 50

51. Urinalysis 8/27/09 ColorDark yellow TransparencyClear pH8 Spec gravity1.015 albuminNegative Sugarnegative Hyaline cast Granular cast RBC0-3/hpf Pus cells0-2/hpf Bacteria fewFew Squamous cells 51

52. Check for rheumatoid factor for coincident occurrence of rheumatoid arthritis Check for autoantibodies Sudden onset is assoc. with HIV so check for HIV disease Nail scrapings – fungal cultures to rule out fungal infection Gram stain and blood culture for bacterial infection Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology 5 th ed 52

53. Synovial Fluid Analysis Fluid GroupColorClarityViscosityMucin ClotCells/mm3% of WBC that are PML NormalPale yellowTransparentHighGood (<200)<25% Group 1 (Non inflammatory) Yellow or straw TransparentHighGood<2,000<25% Group II (Moderately inflammatory Yellow or Straw Transparent to opaque, slightly cloudy Variably decreased Fair to poor 3,000- 50,000 >70% Group III (Highly inflammatory, septic) Variable; yellow-gray, purulent Opaque, cloudyLowPoor50,000- 100,000 (usually <100,000) >75%, close to 100% Group IV (Hemorrhagic) RedOpaqueHighGoodUp to normal count in blood May be the same as normal blood 53

54. 3C-MED RADIOGRAPHIC IMAGING 54

55. DIP involvement – “pencil-in-cup” deformity http://www.hopkins-arthritis.org/arthritis-info/psoriatic-arthritis/diagnosis.html Pencil-in-cup deformity 55

56. Pencil-in-cup deformity Ankylosis Arthritis Mutilans Gladman, D. (2009). Clinical manifestations and diagnosis of psoriatic arthritis. Retrieved September 07, 2009 from http://www.uptodate.com/online/content/topic.do?topicKey=spondylo/2133&view=print 56

57. Asymmetric sacroiliiitis 57

58. spondylitis Severe cervical spine involvement but relative sparing of thoracolumbar spine 58

59. T1-weighted image Short tau inversion recovery (STIR) image Active Inflammation Active sacroiliitis Magnetic resonance imaging in psoriatic arthritis: a review of the literature. Retrieved from http://arthritis- research.com/content/8/2/207/figure/F6 59

60. 3C-MED MANAGEMENT AND TREATMENT 60

61. Treatment Plan Goals Management PharmacologicNon-Pharmacologic Relieve pain NSAIDS Analgesics Paraffin bath Splinting Control Psoriatic Arthritis Biologics DMARDS Rehabilitation Lifestyle Modification Management of Psoriatic Lesions Topical Systemic Phototherapy (PUV-A) Tar Compounds Note Treat secondary infections prior to administration of immunosuppressive agents 61

62. PAIN MANAGEMENT 62

63. Tramadol  Used to manage moderate to moderately severe pain  Mechanism of Action: centrally acting analgesic that binds to μ-opioid receptor and additionally inhibits re- uptake of Norephinephrine and Serotonin  Adverse Effects: anaphylactoid reactions, seizures  Drug Interactions:  Carbamazepine – inc. metabolism  Quinidine – inc. Levels of tramadol  Avoid in patients taking SSRI’s and MAO inhibitors 63

64. According to a study published in the American Journal of Surgery: –Combination tramadol/paracetamol have faster onset, longer duration, and greater pain relief than tramadol or paracetamol alone 64

65. Treatment of Psoriatic Arthritis DrugMOADoseToxicityDrug Interaction Methotrexatedihydrofolate reductase inhibitor Oral 15 – 25 mg/wk Renal dysfunction, Nausea, and Mucosal Ulcers concentration w/ hydroxychloroquine CyclosporineCalcineurin inhibitor Oral 3-5 mg/kg/day 2 doses Nephrotoxicity toxicity with diltiazem, K sparing diuretics and CYP3A inhibitors Etanercept Anti-TNF-α SC 50 mg/wk Macrophage dependent infections, activation of latent TB InfliximabAnti-TNF-αIV 3-5 mg/kg every 8 wks. human anti- chimeric antibodies with MTX AdalimumabAnti-TNF-αSC 40 mg every other week clearance with MTX DMARDS BIOLOGICS 65

66. TREATMENT FOR PSORIATIC ARTHRITIS 66

67. Etanercept Decreases the activity of TNF Often used with methotrexate Mechanism of Action: binds two molecules of TNF (α and β) and prevents them from binding to cellular receptors Adverse Effects: risk of serious infections, neurologic and hematologic events, increased malignant potential, latent TB activation 67

68. –The effectiveness of etanercept, a fusion protein directed against TNF-alpha, in the treatment of psoriatic arthritis is comparable to that of the antibodies. To achieve a marked improvement of the cutaneous manifestations, high doses (50 mg twice weekly) are usually used in the first 12 weeks. 68

69. Infliximab Chimeric IgG К monoclonal antibody composed of human and murine regions Often used with methotrexate MOA: Neutralizes cytokines by binding specifically to TNF-α Adverse Effects: serious infections, hepatotoxicity, hematologic events, hypersensitivity reactions, neurologic events, potential for increased malignancies, latent TB infection 69

70. –Infliximab and adalimumab are therapeutic antibodies directed against TNF-alpha that are highly effective against psoriasis vulgaris and psoriatic arthritis. 70

71. The clinical and radiographic efficacy of adalimumab demonstrated during short-term treatment was sustained during long-term treatment. Adalimumab has a favourable risk– benefit profile in patients with PsA. 71

72. Adalimumab Recombinant monoclonal antibody Mechanism of Action: binds to TNF-α receptor sites, thus inhibiting endogenous TNF-α activity Adverse Effects: serious infections, neurologic events, potential for increased malignancies, hypersensitivity reactions, hematologic events, latent TB infection 72

73. “Tumor necrosis factor (TNF)-alpha inhibitors (infliximab, adalimumab, and etanercept) used in immune-mediated inflammatory diseases such as rheumatoid arthritis, Crohn's disease, or psoriatic arthritis have the potential to increase the risk of infectious complications. Pulmonary infections are one of the most frequent complications associated with the use of TNF inhibitors.” 73

74. Treatment Plan Goals Management PharmacologicNon-Pharmacologic Relieve pain NSAIDS Analgesics Paraffin bath Splinting Control Psoriatic Arthritis Biologics DMARDS Rehabilitation Lifestyle Modification Management of Psoriatic Lesions Topical Systemic Phototherapy (PUV-A) Tar Compounds Note Treat secondary infections prior to administration of immunosuppressive agents 74

75. TREATMENT FOR PSORIASIS 75

76. Alefacept Usually for plaque psoriasis Immunosuppressive dimeric fusion protein Consists of extracellular CD2 binding portion of human leukocyte function MOA: Interferes with lymphocyte activation resulting in the reduction in subsets of CD2 lymphocyte and circulating CD4 and CD8 lymphocyte counts Administration: IM Warnings: Lymphopenia, increased malignancies and serious infections Basic and Clinical Pharmacology, 10 th Ed Harrison’s Principles of Internal Medicine, 17 th Ed 76

77. Efalizumab Usually for SEVERE psoriasis Immunosuppresive recombinant humanized anti CD11a monoclonal antibody MOA: Binding to CD11a inhiits the interaction of LFA-1 on all lymphocutes with intercellular adhesion molecule inhibiting activation, adhesion and migration of T-Lymphocytes into skin Administration: SC injection Warnings: Serious infections, potential increased malignancy, thrombocytopenia, hemolytic anema and worsening of psoriasis * Should not be given with other immunosuppresive medication Basic and Clinical Pharmacology, 10 th Ed Harrison’s Principles of Internal Medicine, 17 th Ed 77

78. Cyclosporine Immunosuppresive agent –Calcineurin inhibitor MOA:Form a complex with cyclophilin that inhibits the cysoplasmic phosphatase, calcineurin, which is necessary for activation of T-cell specific transcription factor Adverse effects: Renal dysfunction, hypertension, hyperkalemia, hyperuricemia, hypomagnesemia, hyperlipidemia, increased risk of malignancies *reported to benefit Psoriatic arthritis Basic and Clinical Pharmacology, 10 th Ed Harrison’s Principles of Internal Medicine, 17 th Ed 78

79. Methotrexate Antimetabolite MOA: Inhibition of dihydrofolate reductase, an enzme important in the production of thymidine and purines –May interfere with actions of interleukin-1 –May also simulate increased release of adenosine, and endogenous anti-inflammatory autocoid –May stimulate apoptosis and death of activated T Lymphocytes Administration: Oral Adverse effects: Hepatotoxicity, pulmonary toxicity, pancytopenia, potential for increased malignancies, ulcerative stomatitis, nausea, diarrhea, teratogenecity Basic and Clinical Pharmacology, 10 th Ed Harrison’s Principles of Internal Medicine, 17 th Ed 79

80. Acitretin Effective in psoriasis (especially pustular forms) Metabolite of etretinate, an aromatic retinoid Retinoids include natural compounds and synthetic derivatives of retinol that exhibit vitamin A activity Because vitamin A affects normal epithelial differentiation, it was investigated as a treatment for cutaneous disorders Administration: Oral Adverse Effects: teratogenecity, osteophyte formation, hyperlipidemia, flare of inflammatory bowel disease, hepatotoxicity and depression * Ethanol should be strictly avoided during treatment and for 2 months after discontinuing therapy Basic and Clinical Pharmacology, 10 th Ed Harrison’s Principles of Internal Medicine, 17 th Ed 80

81. Psoralen with Ultraviolet Light (PUVA) Topically applied or systemically administered psoralens are combined with UV-A Psoralens –Tricyclic furocouramins –intercalated into DNA  exposed to UV-A  form adducts with pyrimidine bases  form DNA crosslinks  decrease DNA synthesis  improvement of psoriasis Adverse Effects: skin dryness, actinic keratoses, increased risk of skin cancer 81

82. –Psoriasis is a very troublesome disease with a high economic impact. The patient has an increased risk of cardiovascular diseases and their complications. Additionally, one out of five patients develops psoriatic arthritis. –MTX and the TNF-alpha antagonists are effective against the cutaneous manifestations of psoriasis. 82

83. Topical Management of Psoriasis –Polytar shampoo –Topical corticoids –Petroleum Jelly –Vitamin D analogues (cacipotriol, tacalcitol) –Other skin care products 83

84. –Topical corticoids of strength classes II and III have a favorable risk/benefit profile when properly used and are also very effective against itching, from which about two- thirds of patients suffer. –A combined preparation consisting of the vitamin D 3 analogue calcipotriol together with a corticoid of intermediate strength, which was studied in a controlled trial over a study interval of an entire year, is very effective and is often used as first-line treatment. 84

85. OBJECTIVES To present a case of a 28 y/o male with Psoriatic Arthritis (PsA) Differential Diagnoses Psoriatic Arthritis –Epidemiology –Pathophysiology –Clinical Features Approach to a Patient with PsA Complications, Outcome and Prognosis of PsA 85

86. 3C-MED COMPLICATION 86

87. Psoriasis Psoriatic Arthritis Cellulitis Risk Factors: Immunocompromised due to meds Auspitz sign – break in skin integrity 87

88. Psoriasis Immunocompromised patient due to medications Auspitz sign Break in the skin integrity Bacteria gains access to the epidermis Acute inflammation of the dermis and subcutaneous tissue Cellulitis Indigenous flora colonizing the skin  Staphylococcus aureus  Streptococcus pyogenes Exogenous bacteria Indigenous flora colonizing the skin  Staphylococcus aureus  Streptococcus pyogenes Exogenous bacteria Harrison’s Principles of Internal Medicine 17 th ed. 88

89. Cellulitis At the involved site –Localized pain –Erythema –Swelling –Warmth –Borders are not sharply demarcated Fever and chills Malaise Harrison’s Principles of Internal Medicine 17 th ed. 89

90. Primary Treatment for Cellulitis Nafcillin or oxacillin, 2 g IV q4 – 6h –Beta Lactam Antibiotics –MOA: interferes with the transpeptidation reaction of bacterial cell wall synthesis –Indications: Susceptible infections due to penicillinase-producing staphylococci. –AE: hypersensitivity –DI: May be antagonized by tetracycline. Potentiated by probenicid. 90

91. Alternative Treatment for Cellulitis Cefazolin 1 g IV q8 –MOA: inhibits cell wall synthesis –Indications: Respiratory, GIT, GUT, otic and bone, skin, soft tissue and post-op infections, bacteremia, septicemia, endocarditis, surgical prophylaxis –AE: Shock, hypersensitivity reaction, granulocytopenia, eosinophilia or thrombocytopenia, GI disturbances, CNS effects –DI: Aminoglycosides, potent diuretics, probenecid 91

92. OBJECTIVES To present a case of a 28 y/o male with Psoriatic Arthritis (PsA) Differential Diagnoses Psoriatic Arthritis –Epidemiology –Pathophysiology –Clinical Features Approach to a Patient with PsA Complications, Outcome and Prognosis of PsA 92

93. Summary Slide A case of a 28 y/o male patient with PsA Psoriatic Arthritis Approach to a Patient with asymmetric polyarthritis Management of Psoriatic Arthritis Complications of Psoriasis - Cellulitis 93

94. THANK YOU! 94