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U.S. 28 year old male, catholic, married, born on May 6, 1981, works as a tricycle driver since 2001, residing in Caloocan City with wife. Chief Complaint: 7 Yrs PTA 2 Yrs PTA 1 Yr PTA •White scales of the scalp resembled dandruff when scratched (no consult) • Few mos. later: pustules and papules that later coalesced to erythematous plaques topped with scales spread all over his body affecting his back, trunk, upper and lower extremities and his face consult at UST Dermatology OPD; punch biopsy: Psoriasis – medications: PUVA therapy (once in 2002), Methotrexate 1 tab BID for 1 wk, Dermovate with Petroleum Jelly and LCD, Hydroxizine (Iterax) for pruritus 3x/day prn resolution of Symptoms • Reappearance of lesions • Painful swelling of distal and proximal joints of the fingers of right and left hands and feet (self-medication: Naproxen temporary relief) • Gradual limitation of in the movement of digits • Consult to Rheumatologist, prescribed with Celebrex and requested for further lab work-ups; but patient lost to follow-up • Pain and swelling in both knees, noted to be limping, and pain when walking down the stairs • Relieved by rest or sitting down 1 month PTA • Swelling of both knees with increasing severity of pain (no consult) 1 week PTA • Pain in the hips extending down to his ankles • More difficulty in ambulating 5 days PTA 4 days PTA • Consulted an Orthopedic Surgeon in Marikina; was told to have excess fluid in knee joints & advised arthrocentesis (pt. opted not to) •Fever [undocumented] (self-medication: Paracetamol temporary lysis of fever) • Persistence of pain and fever consult at FEU Hospital (X-Ray of leg: soft tissue swelling); advised admission but refused due to financial constraints; referred to USTH for further evaluation & management ADMISSION • • • • • • • (-) DM (-) HPN (-) Joint surgery (-) history of trauma (-) Allergy Diagnosed with dengue fever (2nd year high school) Excision of cyst at the back (2007) (+) Myocardial Infarction – father (+) DM – father (-) HPN (-) stroke (-) Psoriasis (-) Cancer (-) Arthrides Smoker: 16-22 y/o (1-2 sticks per day) Occasional Alcoholic Beverage Drinker Denies Illicit Drug Use 3 past sexual partners, all protected 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 General Survey • Conscious, coherent, oriented as to time, place and person, not in cardio-respiratory distress Vital Signs • BP 120/70 mmHg, PR 83 bpm, RR 20 cpm, T 36.6 °C Skin • Warm moist skin, (+) erythematous plaques topped with scales all over the body, (+) hyperpigmented patches over the extremitie, (+) oil spots, (+) nail pitting, (+) onychodystrophy 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 5th 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 Musculoskeletal • (+) sausage-shaped 4th digit of the right hand • (+) swelling and tenderness, both knees, DIP 4th R digit of the hand, R ankle • (+) flexed 5th left digit and the 4th R digit of the hand • Cannot flex the PIP and DIP of the right 2nd digit of the hand Neurological • Conscious, oriented to person, place and time, can follow commands • GCS 15 E4V5M6; pupils 2-3 mm, isocoric ERTL, V1,V2,V3 intact; intact hearing, can swallow, (+) gag reflex, can shrug shoulders, tongue midline on protrusion • Motor: MMT 5/5 on both UE; 4/5 on both LE, no atrophy • Cerebellum: no deficits, can do FTNT, APST, HTST • Sensory: no sensory deficits • DTRs: 2+ on the UE, LE not assessed • (-) Babinski; no nuchal rigidity • • • • • • • • History of Psoriasis Painful swelling of distal and proximal joints of the fingers of right and left hands and feet Gradual limitation of in the movement of digits Pain and swelling in both knees (increasing severity of pain), limping, and pain when walking down the stairs (difficulty in ambulating); Relieved by rest or sitting down Pain in the hips extending down to ankle excess fluid in knee joints Persistence of pain and fever X-ray of leg: soft tissue swelling • • • • • (+) erythematous plaques topped with scales all over the body, (+) hyperpigmented patches over the extremitie, (+) oil spots, (+) nail pitting, (+) onychodystrophy (+) sausage-shaped 4th digit of the right hand (+) swelling and tenderness, both knees, DIP 4th R digit of the hand, R ankle (+) flexed 5th left digit and the 4th R digit of the hand Cannot flex the PIP and DIP of the right 2nd digit of the hand Differential diagnosis Gout Osteoarthritis Reactive Arthritis Rheumatoid Arthritis Septic Arthritis Gout • a common disorder of uric acid metabolism – • • can lead to deposition of monosodium urate (MSU) crystals in soft tissue and recurrent episodes of debilitating joint inflammation if untreated - joint destruction and renal damage definitively diagnosed based on the demonstration of urate crystals in aspirated synovial fluid Gout Physical examination findings: • During an acute gout attack, examine all joints to determine if the patient's arthritis is monoarticular or polyarticular • Involved joints have all the signs of inflammation: swelling, warmth, erythema, and tenderness • The erythema over the joint may resemble cellulitis; the skin may desquamate as the attack subsides • The joint capsule becomes quickly swollen, resulting in a loss of range of motion of the involved joint • During an acute gout attack, patients may be febrile, particularly if it is an attack of polyarticular gout • Look for sites of infection that may have seeded the joint and caused an infectious arthritis that can resemble or coexist with acute gouty arthritis • The presence of tophi suggests long-standing hyperuricemia Osteoarthritis • • • Predominantly involves the weight-bearing joints, including the knees, hips, cervical and lumbosacral spine, and feet Other commonly affected joints - the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints of the hands Cartilage is grossly affected – – Focal ulcerations eventually lead to cartilage loss and eburnation Subchondral bone formation also occurs, with development of bony osteophytes Osteoarthritis Physical examination findings: • Mostly limited to the affected joints • Malalignment with a bony enlargement (depending on the disease severity) may occur • Most cases of osteoarthritis do not involve erythema or warmth over the affected joint(s) – • however, an effusion may be present Limitation of joint motion or muscle atrophy around a more severely affected joint may occur Reactive Arthritis • • • • • • • • • Also known as Reiter syndrome, is an autoimmune condition that develops in response to an infection Usually develops 2-4 weeks after a genitourinary or gastrointestinal infection – recent evidence indicates that a preceding respiratory infection with Chlamydia pneumoniae may also trigger the disease – about 10% of patients do not have a preceding symptomatic infection. Both postvenereal and postenteric forms of reactive arthritis may manifest initially as nongonococcal urethritis Mild dysuria, mucopurulent discharge, prostatitis and epididymitis in men, and vaginal discharge and/or cervicitis in women are other possible manifestations Onset - usually acute and characterized by malaise, fatigue, and fever An asymmetrical, predominately lower-extremity, oligoarthritis - the major presenting symptom Low-back pain occurs in 50% of patients Heel pain is common because of enthesopathies at the Achilles or plantar aponeurosis insertion on the calcaneus The complete Reiter triad of urethritis, conjunctivitis, and arthritis may occur Reactive Arthritis Physical examination findings: • Joints, axial skeleton, entheses – Peripheral joint involvement associated - typically asymmetric and usually affects the weight-bearing joints (ie. knees, ankles, hips), but the shoulders, wrists, and elbows may also be affected – More chronic and severe cases - the small joints of the hands and feet may also be involved; as in other spondyloarthropathies, dactylitis (ie, sausage digits) may develop. – While 50% of patients with reactive arthritis may develop low-back pain, most physical examination findings in patients with acute disease - minimal except for decreased lumbar flexion; patients with more chronic and severe axial disease may develop physical findings similar to ankylosing spondylitis – As with other spondyloarthropathies, the enthesopathy of reactive arthritis may be associated with findings of inflammation (ie. pain, tenderness, swelling) at the Achilles insertion; other sites include the plantar fascial insertion on the calcaneus, ischial tuberosities, iliac crests, tibial tuberosities, and ribs • Skin and nails – Keratoderma blennorrhagica on the palms and soles is indistinguishable from pustular psoriasis - highly suggestive of chronic reactive arthritis – Erythema nodosum may develop but uncommon – Nails can become thickened and crumble, resembling mycotic infection or psoriatic onychodystrophy, but nail pitting is not observed – Circinate balanitis may also develop • Other mucosal signs and symptoms: Painless shiny patches in the palate, tongue, and mucosa of the cheeks and lips have been described Reactive Arthritis Physical examination findings: • Ocular findings – Conjunctivitis - part of the classic triad of Reiter syndrome and can occur before or at the onset of arthritis – Other ocular lesions include acute uveitis (20% of patients), episcleritis, keratitis, and corneal ulcerations; the lesions tend to recur • Enteric infections – May trigger reactive arthritis; pathogens include Salmonella, Shigella, Yersinia, and Campylobacter species; the frequency of reactive arthritis after these enteric infections - about 1-4% – Some patients continue with intermittent bouts of diarrhea and abdominal pain; lesions resembling ulcerative colitis or Crohn disease have been described when ileocolonoscopy is performed in patients with established reactive arthritis • Other manifestations – Mild renal pathology with proteinuria and microhematuria – In severe chronic cases, amyloid deposits and immunoglobulin A (IgA) nephropathy have been reported – Cardiac conduction abnormalities may develop, and aortitis with aortic regurgitation occurs in 1-2% Rheumatoid Arthritis • • • • • • • A chronic systemic inflammatory disease of unknown cause that primarily affects the peripheral joints in a symmetric pattern Constitutional symptoms, including fatigue, malaise, and morning stiffness are common Extra-articular involvement of organs such as the skin, heart, lungs, and eyes can be significant Causes joint destruction and thus often leads to considerable morbidity and mortality Has a significant genetic component, and the shared epitope of the HLA-DR4/DR1 cluster is present in up to 90% of patients with RA, although it is also present in more than 40% of controls Synovial cell hyperplasia and endothelial cell activation are early events in the pathologic process that progresses to uncontrolled inflammation and consequent cartilage and bone destruction Genetic factors and immune system abnormalities contribute to disease propagation Rheumatoid Arthritis Physical examination findings: • Joint involvement - the characteristic feature • In general, the small joints of the hands and feet are affected in a relatively symmetric distribution • The most commonly affected joints, in decreasing frequency, include the MCP, wrist, PIP, knee, MTP, shoulder, ankle, cervical spine, hip, elbow, and temporomandibular joints • Joints show inflammation with swelling, tenderness, warmth, and decreased range of motion • Atrophy of the interosseous muscles of the hands is a typical early finding • Joint and tendon destruction may lead to deformities such as ulnar deviation, boutonnière and swan-neck deformities, hammer toes, and, occasionally, joint ankylosis • Other commonly observed musculoskeletal manifestations – – – tenosynovitis and associated tendon rupture due to tendon and ligament involvement, most commonly involving the fourth and fifth digital extensor tendons at the wrist periarticular osteoporosis due to localized inflammation; generalized osteoporosis due to systemic chronic inflammation, immobilization-related changes, or corticosteroid therapy; and carpal tunnel syndrome most patients have muscle atrophy from disuse, which is often secondary to joint inflammation Septic Arthritis • • • • • Also known as infectious arthritis May represent a direct invasion of joint space by various microorganisms, including bacteria, viruses, mycobacteria, and fungi Reactive arthritis, a sterile inflammatory process, may be the consequence of an infectious process located elsewhere in the body Bacterial pathogens - the most significant because of their rapidly destructive nature Failure to recognize and to appropriately treat septic arthritis results in significant rates of morbidity and may even lead to death Septic Arthritis Physical examination findings: • The most commonly involved joint is the knee (50% of cases), followed by the hip (20%), shoulder (8%), ankle (7%), and wrists (7%) • The elbow, interphalangeal, sternoclavicular, and sacroiliac joints each make up 1-4% of cases • A thorough inspection of all joints for signs of erythema, swelling (90% of cases), warmth, and tenderness is essential for diagnosing infection • Infected joints usually exhibit an obvious effusion, which is associated with marked limitation of both active and passive ranges of motion • Frequently, these findings are apparent but may be diminished or poorly localized in cases of infection of the spine, hip, and shoulder joints • • • • An acute inflammatory condition of the skin characterized by localized pain, erythema, swelling and heat. Caused by indigenous flora colonizing the skin and appendages and exogenous bacteria (e.g. Staphylococcus aureus, Streptococcus pyogenes) May gain access through cracks in the skin, wounds, abrasions, burns Lesions are nodular and surrounded by vesicles that rupture and discharge pus and necrotic material Check for rheumatoid factor for coincident occurence of RA; PsA alone = (-) RF Check also for gout ANA, autoantibodies For seronegative arthritis without skin changes, check for HLA-B13, -BW57, -B27. Sudden onset is assoc. with HIV so check for HIV disease NO diagnostic laboratory tests ESR and CRP often elevated Extensive psoriasis = uric acid may be elevated HLA-B27 is found in 50-70% of patients with axial disease, but <15-20% if only peripheral joint involvement Examine the fluid in joints a. Gross examination – clarity, color b. Cell count – WBC per c. Microscopic examination – crystals, Gram staining d. Culture and sensitivity ** Aspirating needle should never be passed through an overlying cellulitis or psoriatic plaque because of the risk of introducing infection Reference 8/27/09 Hgb 120-170 d/L 105 Hct 0.37-0.54 0.32 RBC 4-6x 10^12/L 4.03 WBC 4.5-10x 10^9/L 8.60 Neutrophil 0.50-0.70 0.70 Segs 0.50-0.70 0.70 Lympho 0.20-0.40 0.30 Mono 0-0.07 Eos 0-0.05 Plt 150-450x 10^9/L 552 MCV 87 +/-5 U^3 79.60 MCH 29+/-2 pg 26.0 MCHC 34+/-2 g/dL 32.70 RDW 25.90 13.40 Bands Reference 8/27/09 BUN 9-23 6.9 Crea 0.5-0.2 0.76 AST-SGOT 0-32 27.3 ALT-SGPT 0-31 41.2 DIP involvement – “pencil-in-cup” deformity marginal erosions of bone and irregular destruction of joint and bone, which, in the phalanx, may give the appearance of a sharpened pencil “whiskering” – marginal erosions with adjacent bony proliferation Small joint ankylosis Osteolysis of phalangeal and metacarpal bone with telescoping of digits Periostitis and proliferative new bone at site of enthesitis Asymmetric sacroiliiitis Less zygoapophyseal joint arthritis, fewer and less symmetric and delicate syndesmophytes Fluffy hyperperiostosis on anterior vertebral bodies Paravertebral ossification Severe cervical spine involvement but relative sparing of thoracolumbar spine Ultrasound and MRI demonstrate enthesitis and tendon sheath effusions Thick S. corneum and projections of the epidermis Parakeratosis(cell nuclei within thickened s. corneum) Elongation of rete ridges PMN leukocyte and lymphocyte infiltration of dermis and epidermis forming microabscesses of Munro in the s.corneum exocytosis of neutrophils into epidermis producing spongiform pustules (Kogoj) Psoriasis Psoriatic Arthritis Cellulitis Psoriasis Psoriatic Arthritis Cellulitis Areas of Predilection Scalp Nails Extensor Surface, Limbs Umbilical region Sacrum Erythematous rash Scaling Plaques Silvery white lamellar Auspitz’s Sign Koebner’s Phenomenon Psoriasis Psoriatic Arthritis Cellulitis An inflammatory arthritis that occurs in a patient with psoriasis. Harrison’s Internal Medicine 17th 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 Unique to Psoriatic Arthritis: DIP joint involvement Nail changes Dactylitis 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 • Patterns of Arthropathy 1. 2. 3. 4. 5. Arthritis of DIP joints Asymmetric oligoarthritis Symmetric polyarthritis Axial involvement Arthritis Mutilans Distal Interphalangeal joint arthritis Occurs in 15 % of cases Nail changes also seen Harrison’s Internal Medicine 17th edition 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 17th edition 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 17th edition Axial Arthropathy Spine and sacroiliac joints Harrison’s Internal Medicine 17th edition 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 17th edition Pitting Horizontal ridging Onycholysis Discoloration of nail margins Dystrophic hyperkeratosis Nail pitting Onycholysis Onychodystrophy Harrison’s Internal Medicine 17th edition Involvement of the distal and proximal interphalangeal joints, together with tendon sheath involvement, may give the digit a sausage shape Harrison’s Internal Medicine 17th edition Inflammation at the sites of ligamentous and tendinous insertions Emedicine Retrieved from: http://emedicine.medscape.com/article/1108557-overview Psoriasis Psoriatic Arthritis Risk Factors: • Immunocompromised due to meds • Auspitz sign – break in skin integrity Cellulitis 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 Indigenous flora colonizing the skin Staphylococcus aureus Streptococcus pyogenes Exogenous bacteria Cellulitis Harrison’s Principles of Internal Medicine 17th ed. At the involved site Localized pain Erythema Swelling Warmth Borders are not sharply demarcated Fever and chills Malaise Harrison’s Principles of Internal Medicine 17th ed. Improve patient’s quality of life Achieve and maintain control of psoriatic lesions Relieve pain Halt progression of disease Alefacept Efalizumab Cyclosporine Methotrexate Acitretin PUVA • • • • • • Usually for treatment of 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, 10th Ed Harrison’s Principles of Internal Medicine, 17th Ed • • • • • 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, 10th Ed Harrison’s Principles of Internal Medicine, 17th Ed • 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, 10th Ed Harrison’s Principles of Internal Medicine, 17th Ed • • Antimetabolite MOA: Inhibition of dihydrofolate reductase, an enzme important in the production of thymidine and purines – – – • • May interere 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, panctopenia, potential for increased malignancies , ulcerative stomatitis, nausea, diarrhea, teratogenecity Basic and Clinical Pharmacology, 10th Ed Harrison’s Principles of Internal Medicine, 17th Ed • • • 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, 10th Ed Harrison’s Principles of Internal Medicine, 17th Ed 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 basesform DNA crosslinksdecrease DNA synthesisimprovement of psoriasis Adverse Effects: skin dryness, actinic keratoses, increased risk of skin cancer Etanercept Infliximab Adalimumab Tramadol 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 Chimeric IgGК monoclonal antibody composed of human and murine regions Often used with methotrexate Mechanism of Action: Neutralizes cytokines by binding specifically to TNF-α Adverse Effects: serious infections, hepatotoxicity, hematologic events, hypersensitivity reactions, neurologic events, potential for increased malignancies 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 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