1. AUTOIMMUNE PATHOLOGY
1.1. SERONEGATIVE SPONDYLOARTHROPATHIES
1.1.1. SERONEGATIVE SPONDYLOARTHROPATHIES ARE A GROUP OF JOINT DISORDERS CHARACTERIZED BY:
1.1.1.1. ARTHRITIS WITHOUT RHEUMATOID FACTOR (ANTI-IGG ANTIBODY), HENCE “SERONEGATIVE”
1.1.1.2. STRONG ASSOCIATION WITH HLA-B27
1.1.1.3. AXIAL SKELETON INVOLVEMENT, HENCE “SPONDYLO-”
1.1.2. SERONEGATIVE SPONDYLOARTHROPATHIES INCLUDE PSORIATIC ARTHRITIS, ANKYLOSING SPONDYLITIS, ARTHROPATHY ASSOCIATED WITH INFLAMMATORY BOWEL DISEASE, AND REACTIVE ARTHRITIS (REITER SYNDROME)
1.1.2.1. A HELPFUL MNEMONIC FOR REMEMBERING THE SERONEGATIVE SPONDYLOARTHROPATHIES IS PAIR:
1.1.2.1.1. P – PSORIATIC ARTHRITIS
1.1.2.1.2. A – ANKYLOSING SPONDYLITIS
1.1.2.1.3. I – INFLAMMATORY BOWEL DISEASE
1.1.2.1.4. R – REACTIVE ARTHRITIS (REITER SYNDROME)
1.1.3. ANKYLOSING SPONDYLITIS
1.1.3.1. CHRONIC DEGENERATIVE INFLAMMATORY ARTHRITIS PRIMARILY AFFECTING THE SPINE AND SACROILIAC JOINTS
1.1.3.2. TYPICALLY SEEN IN YOUNG ADULT MALES (20S-30S)
1.1.3.3. THE PATHOPHYSIOLOGY PROGRESSES THROUGH THREE PHASES:
1.1.3.3.1. FIRST, THERE IS DEVELOPMENT OF SYNOVITIS (INFLAMMATION OF THE SYNOVIA) AND ENTHESITIS (INFLAMMATION OF THE ENTHESES – STRUCTURES THAT ATTACH LIGAMENTS AND TENDONS TO BONE)
1.1.3.3.2. NEXT, BONE DESTRUCTION (MEDIATED BY OSTEOCLASTS, CATHEPSIN K, AND METALLOPROTEINASES) DEVELOPS ALONGSIDE BONE PRODUCTION WITH FORMATION OF SYNDESMOPHYTES (BONY GROWTHS ORIGINATING INSIDE LIGAMENTS) AT THE SITES OF SYNOVITIS AND ENTHESITIS
1.1.3.3.3. EVENTUALLY, THERE IS SPINAL FUSION WHICH IS CLASSICALLY CHARACTERIZED ON X-RAY AS A "BAMBOO SPINE"
1.1.3.4. EXTRA-ARTICULAR MANIFESTATIONS ARE COMMON AND INCLUDE:
1.1.3.4.1. UVEITIS
1.1.3.4.2. AORTITIS
1.1.3.4.3. DECREASED CHEST EXPANSION
1.1.3.5. TREATMENT CONSISTS OF PHYSICAL THERAPY AND MEDICATIONS WHICH INCLUDE:
1.1.3.5.1. NSAIDS ARE FIRST LINE (PARTICULARLY INDOMETHACIN)
1.1.3.5.2. CORTICOSTEROIDS
1.1.3.5.3. DISEASE MODIFYING AGENTS (E.G. METHOTREXATE, CYCLOSPORINE)
1.1.3.5.4. TNF-ALPHA INHIBITORS
1.1.4. REACTIVE ARTHRITIS (FORMERLY KNOWN AS REITER SYNDROME)
1.1.4.1. ASYMMETRIC INFLAMMATORY OLIGOARTHRITIS THAT DEVELOPS 1-4 WEEKS AFTER EITHER A NONGONOCOCCAL URETHRITIS OR AN INFECTIOUS DIARRHEA
1.1.4.2. CHARACTERIZED BY THE SYMPTOMATIC TRIAD OF ARTHRITIS (USUALLY INVOLVING JOINTS IN THE LOWER EXTREMITIES), URETHRITIS, AND NON-INFECTIOUS CONJUNCTIVITIS
1.1.4.2.1. A HELPFUL MNEMONIC TO REMEMBER THESE SYMPTOMS IS: “CAN’T PEE, CAN’T SEE, CAN’T CLIMB A TREE.”
1.1.4.3. IN ADDITION TO THE CLASSIC SYMPTOMATIC TRIAD OF URETHRITIS, CONJUNCTIVITIS, AND ARTHRITIS, PATIENTS WITH REACTIVE ARTHRITIS FREQUENTLY DEVELOP:
1.1.4.3.1. ORAL ULCERS
1.1.4.3.2. KERATODERMA BLENNORRHAGICA
1.1.4.3.3. CIRCINATE BALANITIS
1.1.4.4. TWO SUBTYPES: POSTVENEREAL REACTIVE ARTHRITIS AND POSTENTERIC REACTIVE ARTHRITIS
1.1.4.4.1. POSTVENERAL REACTIVE ARTHRITIS OCCURS AFTER NONGONOCOCCAL URETHRITIS AND IS MOST COMMONLY ASSOCIATED WITH A CHLAMYDIA TRACHOMATIS INFECTION, BUT CAN ALSO BE DUE TO UREAPLASMA UREALYTICUM
1.1.4.4.2. POSTENTERIC REACTIVE ARTHRITIS OCCURS AFTER AN INFECTIOUS DIARRHEA AND IS MOST COMMONLY ASSOCIATED WITH:
1.1.4.4.3. A HELPFUL MNEMONIC TO REMEMBER THE ORGANISMS ASSOCIATED WITH REACTIVE ARTHRITIS (POSTVENERAL AND POSTENTERIC) IS “U CCSSY,” WHICH SHOULD BE READ AS “YOU SISSY:”
1.1.5. PSORIATIC ARTHRITIS
1.1.5.1. ASYMMETRIC INFLAMMATORY POLYARTHRITIS THAT AFFECTS 10-30% OF PEOPLE SUFFERING FROM PSORIASIS
1.1.5.2. IT USUALLY INVOLVES THE AXIAL AND PERIPHERAL JOINTS, WITH THE DIP JOINTS OF THE HANDS AND FEET MOST COMMONLY AFFECTED
1.1.5.2.1. SWELLING OF THE DIP JOINTS LEADS TO FINGERS APPEARING “SAUSAGE-SHAPED.”
1.1.5.2.2. TELESCOPING OF ONE PHALANX INTO ANOTHER AT THE DIP CAN ALSO OCCUR AND LEADS TO A CHARACTERISTIC “PENCIL-IN-CUP” DEFORMITY ON X-RAY
1.1.5.2.3. EXTENSIVE NAIL PITTING MAY ALSO BE SEEN
1.1.5.3. TREATMENT IS AIMED AT REDUCING THE UNDERLYING INFLAMMATORY PROCESSES
1.1.5.3.1. FIRST LINE THERAPY INCLUDES ANTI-INFLAMMATORY AGENTS LIKE NSAIDS (E.G. DICLOFENAC, NAPROXEN)
1.2. DERMATOMYOSITIS (DM) & POLYMYOSITIS (PM)
1.2.1. NONINFECTIOUS INFLAMMATORY MYOPATHIES THAT PRESENT WITH SYMMETRIC PROXIMAL MUSCLE WEAKNESS; NORMAL REFLEXES, NORMAL SENSATION
1.2.1.1. BOTH DM AND PM ARE MORE COMMON IN WOMEN THAN MEN
1.2.1.1.1. PEAK INCIDENCE IN ADULTS 40 – 50 YEARS OF AGE
1.2.1.2. IN DM THERE IS SKIN INVOLVEMENT; IN PM THE SKIN IS NOT INVOLVED
1.2.1.3. DM CAN MANIFEST AS A PARANEOPLASTIC SYNDROME ASSOCIATED WITH CARCINOMAS
1.2.1.3.1. PARTICULARLY GASTRIC, COLORECTAL, AND BRONCHOGENIC CARCINOMAS
1.2.1.4. PM CAN ALSO MANIFEST AS A PARANEOPLASTIC SYNDROME
1.2.1.4.1. PARTICULARLY IN ASSOCIATION WITH LUNG CANCER
1.2.2. SKIN INVOLVEMENT IN DM (NOT SEEN IN PM):
1.2.2.1. GOTTRON’S SIGN
1.2.2.1.1. ERYTHEMATOUS SCALY ERUPTION OR DUSKY PURPLE PATCHES OVER THE EXTENSOR SURFACES OF THE KNUCKLES (METACARPOPHALANGEAL AND/OR INTERPHALANGEAL JOINTS), ELBOWS, AND KNEES
1.2.2.2. HELIOTROPE RASH (“RACOON EYES”)
1.2.2.2.1. LILAC OR VIOLACEOUS EYELID DISCOLORATION WITH PERIORBITAL EDEMA
1.2.2.3. SHAWL SIGN
1.2.2.3.1. ERYTHEMA OF THE CHEST AND SHOULDERS
1.2.2.4. V-SIGN
1.2.2.4.1. ERYTHEMA IN A V-SHAPED DISTRIBUTION OVER THE ANTERIOR NECK AND CHEST
1.2.3. DEFINITIVE DIAGNOSIS OF DM OR PM REQUIRES MUSCLE BIOPSY
1.2.3.1. DM: ANTIBODY-MEDIATED DAMAGE OF BLOOD VESSELS SURROUNDING MUSCLE FASCICLES (IN THE PERIMYSIAL CONNECTIVE TISSUE)
1.2.3.1.1. → PERIFASCICULAR INFLAMMATION AND ATROPHY
1.2.3.2. PM: CELL-MEDIATED (CD8 CYTOTOXIC T CELLS AND MACROPHAGES) DAMAGE OF MUSCLE FIBERS
1.2.3.2.1. → ENDOMYSIAL INFLAMMATION (NECROTIC AND REGENERATING MUSCLE FIBERS SCATTERED THROUGHOUT THE FASCICLE, NOT LIMITED TO THE FASCICLE PERIPHERY AS IN DM)
1.2.4. LABS AND TESTS:
1.2.4.1. ↑ SERUM CK (CREATINE KINASE)
1.2.4.2. ↑ SERUM ALDOLASE
1.2.4.3. POSITIVE ANTI-JO-1 IN 25% OF PATIENTS
1.2.4.3.1. ANTIBODY AGAINST HISTIDYL-TRNA-SYNTHETASE ANTIGEN
1.2.4.3.2. CONSIDERED A MYOSITIS-SPECIFIC AUTOANTIBODY
1.2.4.4. POSITIVE ANA IN 40-60% OF PATIENTS
1.2.4.4.1. NOT SPECIFIC TO DM OR PM
1.2.4.5. EMG: VOLUNTARY ACTIVATION OF MUSCLE
1.2.4.5.1. → SHORT-DURATION, LOW-AMPLITUDE POLYPHASIC MOTOR POTENTIALS
1.2.5. TREATMENT
1.2.5.1. GLUCOCORTICOIDS (EG, PREDNISONE) WITH OR WITHOUT GLUCOCORTICOID-SPARING AGENTS (AZATHIOPRINE, METHOTREXATE)
1.3. SYSTEMIC SCLEROSIS (SCLERODERMA)
1.3.1. CHRONIC DISEASE WITH LIKELY AUTOIMMUNE ETIOLOGY CHARACTERIZED BY:
1.3.1.1. 1. WIDESPREAD MICROVASCULAR DAMAGE
1.3.1.2. 2. EXCESSIVE INTERSTITIAL AND PERIVASCULAR COLLAGEN DEPOSITION (FIBROSIS/SCLEROSIS)
1.3.2. UNKNOWN ANTIGEN(S) MAY STIMULATE LYMPHOCYTES TO RELEASE CYTOKINES (EG, TGF-Β, IL-13)
1.3.2.1. → ↑ FIBROBLAST PRODUCTION OF COLLAGEN, FIBRONECTIN, AND OTHER EXTRACELLULAR MATRIX PROTEINS
1.3.3. SKIN UNDERGOES SCLEROTIC ATROPHY
1.3.3.1. → HARD/SWOLLEN/TIGHT-APPEARING SKIN WITH FEWER WRINKLES
1.3.3.1.1. → MASK-LIKE FACIES AND CLAW-LIKE HANDS
1.3.4. ISCHEMIA SECONDARY TO VASCULITIS OF SMALL ARTERIES AND CUTANEOUS ARTERIOLES MAY CAUSE CUTANEOUS ULCERATION IN THE FINGERS/TOES
1.3.5. MOST COMMON INITIAL FINDING IN SYSTEMIC SCLEROSIS IS RAYNAUD’S PHENOMENON SECONDARY TO DIGITAL VASCULITIS
1.3.5.1. REYNAUD'S PHENOMENON IS VASOCONSTRICTION LEADING TO REDUCED BLOOD FLOW IN THE DIGITS AND EXTREMITIES IN RESPONSE TO COLD OR EMOTIONAL STRESS
1.3.6. MOST COMMON VISCERAL COMPLICATION OF SYSTEMIC SCLEROSIS - SEEN IN 90% OF CASES - IS ESOPHAGEAL DYSFUNCTION (E.G - DYSMOTILITY)
1.3.7. THERE ARE TWO TYPES OF SYSTEMIC SCLEROSIS:
1.3.7.1. DIFFUSE SYSTEMIC SCLEROSIS:
1.3.7.1.1. DIFFUSE SCLEROSIS OF SKIN AT ONSET
1.3.7.1.2. EARLY VISCERAL INVOLVEMENT
1.3.7.1.3. DIFFUSE SYSTEMIC SCLEROSIS CAUSES EXTENSIVE VISCERAL DAMAGE, PARTICULARLY TO THE:
1.3.7.2. LIMITED SYSTEMIC SCLEROSIS:
1.3.7.2.1. LIMITED SCLEROSIS OF SKIN AT ONSET (FINGERS, FOREARM, FACE)
1.3.7.2.2. LATE OR NO VISCERAL INVOLVEMENT
1.3.7.2.3. A SUBSET OF PATIENTS WITH LIMITED SYSTEMIC SCLEROSIS DEVELOP CREST SYNDROME:
1.3.8. SERUM AUTOANTIBODIES:
1.3.8.1. ANTIBODIES AGAINST DNA TOPOISOMERASE I (ANTI-SCL-70) AND RNA POLYMERASE III (ANTI-RNA POL-III) ARE MORE COMMON IN DIFFUSE SYSTEMIC SCLEROSIS
1.3.8.1.1. ANA IS ALSO ASSOCIATED WITH SYSTEMIC SCLEROSIS
1.3.8.2. ANTICENTROMERE ANTIBODIES ARE MORE COMMON IN CREST SYNDROME (WHICH OCCURS IN A SUBSET OF PATIENTS WITH LIMITED SYSTEMIC SCLEROSIS)
1.3.8.3. ANA IS POSITIVE IN 70-90% OF PATIENTS WITH DIFFUSE OR LIMITED SYSTEMIC SCLEROSIS
1.4. POLYMYALGIA RHEUMATICA
1.4.1. INFLAMMATORY RHEUMATIC DISORDER OF THE SYNOVIUM, BURSA, AND TENOSYNOVIUM
1.4.2. MORE COMMON IN WOMEN GREATER THAN 50 YEARS OLD
1.4.3. PRIMARY SYMPTOMS OF POLYMYALGIA RHEUMATICA INCLUDE PAIN AND STIFFNESS OF THE NECK, TORSO, SHOULDERS, AND HIPS
1.4.3.1. THE PAIN AND STIFFNESS IS OFTEN BILATERAL
1.4.3.2. SYSTEMIC SYMPTOMS LIKE FEVER, MALAISE, AND WEIGHT LOSS MAY ALSO BE PRESENT
1.4.3.3. MUSCLE STRENGTH IS NORMAL BECAUSE PAIN IS USUALLY DUE TO BURSITIS OR TENOSYNOVITIS (AND NOT MYOSITIS)
1.4.3.4. LAB VALUES SHOW:
1.4.3.4.1. INCREASED ERYTHROCYTE SEDIMENTATION RATE (ESR)
1.4.3.4.2. INCREASED C-REACTIVE PROTEIN
1.4.3.4.3. NORMAL CREATININE KINASE (CK), DUE TO NO MYOSITIS
1.4.4. ASSOCIATED WITH TEMPORAL (GIANT CELL) ARTERITIS
1.4.5. RAPID RESPONSE TO LOW-DOSE CORTICOSTEROIDS (E.G. PREDNISONE)
1.5. SARCOIDOSIS
1.5.1. SYSTEMIC GRANULOMATOUS DISEASE OF UNKNOWN ETIOLOGY THAT MOST COMMONLY INVOLVES THE LUNGS, SKIN, AND/OR EYES, BUT MAY ALSO INVOLVE LIVER, KIDNEY, AND HEART
1.5.1.1. SARCOIDOSIS IS CHARACTERIZED BY NON-CASEATING GRANULOMAS
1.5.2. IT MOST COMMONLY AFFECTS YOUNG TO MIDDLE-AGED BLACK WOMEN WITH PEAK INCIDENCE BETWEEN 20-29 YEARS OF AGE
1.5.2.1. THERE IS A SECOND PEAK IN INCIDENCE IN BLACK WOMEN OVER 50
1.5.3. SARCOIDOSIS MOST COMMONLY INVOLVES:
1.5.3.1. LUNG:
1.5.3.1.1. INTERSTITIAL INFLAMMATION → FIBROSIS → RESTRICTIVE LUNG DISEASE
1.5.3.1.2. CHEST X-RAY
1.5.3.2. SKIN:
1.5.3.2.1. ERYTHEMA NODOSUM
1.5.3.2.2. EPITHELIAL GRANULOMAS CONTAINING MICROSCOPIC SCHAUMANN BODIES AND ASTEROID BODIES
1.5.3.3. EYES:
1.5.3.3.1. ANTERIOR UVEITIS
1.5.4. SARCOIDOSIS IS FREQUENTLY ASSOCIATED WITH HYPERCALCEMIA:
1.5.4.1. MACROPHAGES INSIDE THE GRANULOMAS CONVERT VITAMIN D TO ITS ACTIVE FORM, RESULTING IN ELEVATED LEVELS OF 1,25-DIHYDROXYVITAMIN D
1.5.4.2. SYMPTOMS OF SARCOIDOSIS-ASSOCIATED HYPERCALCEMIA INCLUDE:
1.5.4.2.1. BONE PAIN
1.5.4.2.2. KIDNEY STONES
1.5.4.2.3. ABDOMINAL PAIN
1.5.4.2.4. ANXIETY AND/OR ALTERED MENTAL STATUS
1.5.4.2.5. A MNEMONIC IS: "BONES, STONES, GROANS, AND PSYCHIATRIC OVERTONES."
1.5.5. LAB: ↑ SERUM LEVELS OF:
1.5.5.1. ACE (ANGIOTENSIN CONVERTING ENZYME)
1.5.5.2. CALCIUM (IE, HYPERCALCEMIA)
1.5.5.3. GAMMAGLOBULINS (IE, HYPERGAMMAGLOBULINEMIA)
1.6. SJÖGREN SYNDROME
1.6.1. LYMPHOCYTE-MEDIATED AUTOIMMUNE DESTRUCTION (TYPE IV HYPERSENSITIVITY) OF MINOR SALIVARY AND LACRIMAL GLANDS THAT CAN LEAD TO ATROPHY AND FIBROSIS
1.6.2. IT CLASSICALLY PRESENTS IN OLDER WOMEN (40-60 YEARS)
1.6.3. IT CLASSICALLY PRESENTS AS THE TRIAD OF:
1.6.3.1. KERATOCONJUNCTIVITIS SICCA (DRY EYES)
1.6.3.1.1. IT CAN LEAD TO CORNEAL DAMAGE AND CONJUNCTIVITIS
1.6.3.2. XEROSTOMIA (DRY MOUTH)
1.6.3.2.1. IT CAN LEAD TO INCREASED ORAL BACTERIA AND RECURRENT DENTAL CARIES, DUE TO DECREASED SALIVARY CIRCULATION
1.6.3.3. RHEUMATOID ARTHRITIS
1.6.4. A PATIENT WITH CLASSIC SJÖGREN’S SYNDROME MAY COMPLAIN OF “SAND IN MY EYE AND I CAN’T CHEW A CRACKER” DUE TO THEIR KERATOCONJUNCTIVITIS AND XEROSTOMIA, RESPECTIVELY
1.6.5. SICCA SYNDROME ALSO PRESENTS WITH KERATOCONJUNCTIVITIS (DRY EYES) AND XEROSTOMIA (DRY MOUTH), BUT UNLIKE SJÖGREN’S SYNDROME, HAS NO ARTHRITIS
1.6.6. PHYSICAL EXAM FINDINGS OF A PATIENT WITH SJÖGREN’S SYNDROME MAY INCLUDE BILATERAL PAROTID GLAND ENLARGEMENT
1.6.7. IN MOST CASES OF SJÖGREN’S SYNDROME, LABORATORY FINDINGS ARE CHARACTERIZED BY
1.6.7.1. ANTI-SS-A (ANTI-RO) (ANTI-RIBONUCLEOPROTEIN ANTIBODY)
1.6.7.2. ANTI-SS-B (ANTI-LA) (ANTI-RIBONUCLEOPROTEIN ANTIBODY)
1.6.7.3. ANA (ANTI-NUCLEAR ANTIBODY)
1.6.8. THE MOST ACCURATE TEST CONFIRMING SJÖGREN’S SYNDROME IS LIP BIOPSY DEMONSTRATING LYMPHOID DESTRUCTION OF THE MINOR SALIVARY GLANDS
1.6.9. SCHIRMER’S TEST MEASURES THE OUTPUT OF THE LACRIMAL GLAND TO DETERMINE IF ENOUGH TEARS ARE BEING PRODUCED
1.6.9.1. FILTER PAPER STRIPS INSERTED INTO THE EYES SHOWING LESS THAN 5 MM OF MOISTURE IN 5 MINUTES IS HIGHLY SUGGESTIVE OF SJÖGREN’S SYNDROME
1.6.10. SJOGREN’S SYNDROME LEADS TO AN INCREASED RISK FOR B-CELL (MARGINAL ZONE) LYMPHOMA WHICH PRESENTS AS UNILATERAL ENLARGEMENT OF THE PAROTID GLAND LATE IN DISEASE COURSE
1.6.10.1. MALIGNANCY IS THE MOST COMMON CAUSE OF DEATH IN PATIENTS WITH SJÖGREN’S SYNDROME
1.6.11. ANTI-RO/SS-A AND/OR ANTI-LA/SS-B ANTIBODIES MAY CROSS THE PLACENTA AND MEDIATE AUTOIMMUNE DESTRUCTION OF THE NEONATE’S ATRIOVENTRICULAR (AV) NODE AND CARDIAC CONDUCTION SYSTEM
1.6.11.1. → CONGENITAL THIRD DEGREE (COMPLETE) HEART BLOCK
1.6.12. TREATMENT
1.6.12.1. SYMPTOMATIC, PARTICULARLY IN THE MANAGEMENT OF DRY EYES AND DRY MOUTH
1.6.12.1.1. DRY EYES CAN BE TREATED WITH:
1.6.12.1.2. CEVIMELINE (CHOLINERGIC AGENT WITH MUSCARINIC AGONIST ACTIVITY) CAN BE USED TO TREAT DRY MOUTH
1.7. RHEUMATOID ARTHRITIS
1.7.1. RA (RHEUMATOID ARTHRITIS) IS A CHRONIC SYSTEMIC AUTOIMMUNE DISEASE:
1.7.2. STRONG ASSOCIATION WITH HLA-DR4
1.7.3. OCCURS 3 TIMES MORE OFTEN IN WOMEN THAN MEN
1.7.4. AGE OF ONSET TYPICALLY BETWEEN 30 AND 50 YEARS OF AGE
1.7.5. RA (RHEUMATOID ARTHRITIS) PATIENTS TYPICALLY PRESENT WITH:
1.7.5.1. 1) MORNING STIFFNESS WHICH IMPROVES WITH USE AS THE DAY PROGRESSES
1.7.5.1.1. VS. OSTEOARTHRITIS, WHICH IS AGGRAVATED BY USE AND WORSENS AS THE DAY PROGRESSES
1.7.5.2. 2) SYMMETRIC INVOLVEMENT OF MULTIPLE JOINTS (WHICH BECOME WARM, PAINFUL, SWOLLEN), USUALLY THE SMALL JOINTS OF THE HANDS AND FEET
1.7.5.2.1. WHEN RHEUMATOID ARTHRITIS AFFECTS THE HAND, TYPICALLY THERE IS MCP AND PIP JOINT INVOLVEMENT WITH SPARING OF THE DIP JOINTS — VERSUS OSTEOARTHRITIS WHICH USUALLY INVOLVES THE PIP AND DIP JOINTS BUT SPARES THE MCP JOINTS
1.7.5.3. 3) SYSTEMIC S/SXS — FOR EXAMPLE:
1.7.5.3.1. FEVER, FATIGUE, MALAISE, ANOREXIA
1.7.5.3.2. PLEURITIS, PERICARDITIS
1.7.6. THE ETIOLOGY OF RHEUMATOID ARTHRITIS REMAINS UNKNOWN
1.7.6.1. HOWEVER, INFECTIOUS AGENTS (EG, EBV, HHV6, PARVOVIRUS, MYCOPLASMA) MAY PLAY A ROLE IN THE INITIAL INSULT, TRIGGERING AN IMMUNE REACTION AGAINST NORMAL HOST TISSUES (EG, SOFT TISSUES, SYNOVIAL MEMBRANES, CARTILAGE, BONE)
1.7.7. PATHOGENESIS
1.7.7.1. REGARDLESS OF ETIOLOGY, AUTOIMMUNITY PLAYS A CENTRAL ROLE IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS:
1.7.7.1.1. SYNOVIAL CELLS (POSSIBLY DAMAGED BY AN INFECTIOUS AGENT OR CELL-MEDIATED AUTOIMMUNITY) MAY EXPRESS AN ANTIGEN THAT STIMULATES PLASMA CELLS TO PRODUCE RHEUMATOID FACTOR (RF, AN IGM ANTIBODY THAT BINDS THE FC PORTION OF IGG)
1.7.7.2. LATE/CHRONIC STAGES
1.7.7.2.1. CHRONIC AUTOIMMUNE DESTRUCTION →
1.7.8. LABS:
1.7.8.1. SERUM AUTO-ANTIBODIES:
1.7.8.1.1. RHEUMATOID FACTOR (RF) IS THE MOST COMMON AND IS FOUND IN 80% OF PATIENTS; RF IS ALSO ASSOCIATED WITH INCREASED MORBIDITY
1.7.8.1.2. ANTI-CCP IS MORE SPECIFIC BUT LESS SENSITIVE THAN RF
1.7.8.1.3. ANA IN 30% OF PATIENTS
1.7.8.2. SYNOVIAL FLUID:
1.7.8.2.1. ↓ VISCOSITY
1.7.8.2.2. ↓ C3
1.7.8.2.3. ↑ WBCS
1.7.8.3. INFLAMMATION:
1.7.8.3.1. ↑ ESR (ERYTHROCYTE SEDIMENTATION RATE)
1.7.8.3.2. ↑ CRP (C-REACTIVE PROTEIN)
1.7.8.3.3. SERUM PROTEIN ELECTROPHORESIS:
1.7.9. THERAPY
1.7.9.1. FIRST-LINE THERAPY:
1.7.9.1.1. NSAIDS
1.7.9.1.2. DMARDS (DISEASE-MODIFYING ANTIRHEUMATIC DRUGS)
1.7.9.2. SECOND-LINE THERAPY:
1.7.9.2.1. TNF-Α INHIBITORS
1.7.9.2.2. LEFLUNOMIDE
1.7.9.2.3. RITUXIMAB
1.8. EXTRA-ARTICULAR MANIFESTATIONS IN RHEUMATOID ARTHRITIS
1.8.1. EXTRA-ARTICULAR MANIFESTATIONS IN RHEUMATOID ARTHRITIS (RA) ARE COMMON, OCCURRING IN AN ESTIMATED 40% OF PATIENTS
1.8.2. RHEUMATOID NODULES ARE FIRM TISSUE SWELLINGS THAT OCCUR IN ASSOCIATION WITH RHEUMATOID ARTHRITIS
1.8.2.1. THE PRESENCE OF RHEUMATOID NODULES CORRELATES WITH A HIGH RHEUMATOID FACTOR (RF) TITER
1.8.2.2. THE HISTOPATHOLOGY OF RHEUMATOID NODULES CONSISTS OF A CENTRAL FIBRINOID NECROSIS SURROUNDED BY A RIM OF PALISADING HISTIOCYTES AND A CHRONIC LYMPHOCYTIC INFILTRATE
1.8.2.3. RHEUMATOID NODULES ARE MOST OFTEN LOCATED IN THREE COMMON SITES BENEATH THE SKIN:
1.8.2.3.1. EXTENSOR SURFACE OF THE FINGERS/HAND
1.8.2.3.2. EXTENSOR SURFACES OF THE FOREARM/ELBOW
1.8.2.3.3. OVERLYING THE CALCANEAL TUBEROSITY
1.8.2.4. RHEUMATOID NODULES MAY ALSO BE LOCATED IN THE LUNGS
1.8.3. HEMATOLOGIC MANIFESTATIONS OF RHEUMATOID ARTHRITIS INCLUDE ANEMIA OF CHRONIC DISEASE AND FELTY SYNDROME
1.8.3.1. RA-ASSOCIATED ANEMIA OF CHRONIC DISEASE CAN RESULT IN THE FOLLOWING LAB VALUE CHANGES:
1.8.3.1.1. DECREASED SERUM FE
1.8.3.1.2. INCREASED SERUM FERRITIN
1.8.3.1.3. DECREASED SERUM TRANSFERRIN (TIBC)
1.8.3.2. FELTY SYNDROME IS A DISORDER COMPRISED OF:
1.8.3.2.1. RHEUMATOID ARTHRITIS (RA)
1.8.3.2.2. SPLENOMEGALY
1.8.3.2.3. LEUKOPENIA (AUTOIMMUNE NEUTROPENIA)
1.8.3.3. THE ETIOLOGY OF FELTY SYNDROME IS UNKNOWN BUT IS MORE COMMON IN PATIENTS WHO HAVE HAD RHEUMATOID ARTHRITIS FOR A LONG TIME
1.8.4. PULMONARY MANIFESTATIONS OF RHEUMATOID ARTHRITIS (RA) INCLUDE:
1.8.4.1. PLEURITIS WITH PLEURAL EFFUSIONS
1.8.4.2. INTERSTITIAL FIBROSIS
1.8.4.3. CAPLAN SYNDROME
1.8.4.3.1. CAPLAN SYNDROME IS A DISORDER COMPRISED OF:
1.8.5. CARDIOVASCULAR MANIFESTATIONS OF RHEUMATOID ARTHRITIS (RA) ARE DUE TO CHRONIC INFLAMMATION AND INCLUDE:
1.8.5.1. CARDITIS (PERICARDITIS, MYOCARDITIS, ENDOCARDITIS)
1.8.5.2. VASCULITIS (NOTABLY, AORTITIS)
1.8.5.3. ATHEROSCLEROSIS (LEADING TO INCREASED PERIPHERAL ARTERY DISEASE)
1.8.6. NEUROLOGIC MANIFESTATIONS OF RHEUMATOID ARTHRITIS (RA) INCLUDE:
1.8.6.1. CARPAL TUNNEL SYNDROME
1.8.6.1.1. CARPAL TUNNEL SYNDROME (CTS) IS THE MOST COMMON NEUROLOGIC COMPLICATION IN RHEUMATOID ARTHRITIS (RA)
1.8.6.1.2. CARPAL TUNNEL SYNDROME IN RHEUMATOID ARTHRITIS IS LIKELY DUE TO FINGER-FLEXOR TENOSYNOVITIS, BUT MAY ALSO BE CAUSED BY MEDIAN NERVE COMPRESSION SECONDARY TO JOINT DAMAGE, DEFORMITY, AND SWELLING NEAR THE WRIST
1.8.6.2. ATLANTOAXIAL JOINT SUBLUXATION
1.8.6.2.1. ATLANTOAXIAL JOINT SUBLUXATION IS DUE TO EROSION OF THE DENS (ODONTOID PROCESS) OF THE AXIS, THE ATLAS, OR THE TRANSVERSE LIGAMENT OF THE ATLAS (THE 3 COMPONENTS OF THE MEDIAN ATLANTO-AXIAL JOINTS OF THE CERVICAL SPINE)
1.8.6.3. ISCHEMIC STROKE
1.8.6.3.1. ISCHEMIC STROKE IS LIKELY DUE TO INCREASED ATHEROSCLEROSIS THAT OCCURS IN RHEUMATOID ARTHRITIS, BUT MAY ALSO OCCUR SECONDARY TO ATLANTOAXIAL JOINT SUBLUXATION
1.8.7. SJÖGREN SYNDROME:
1.8.7.1. DRY EYES (KERATOCONJUNCTIVITIS SICCA) DUE TO AUTOIMMUNE DESTRUCTION OF LACRIMAL GLANDS
1.8.7.2. DRY MOUTH (XEROSTOMIA) DUE TO AUTOIMMUNE DESTRUCTION OF SALIVARY GLANDS LEADS TO INCREASED INCIDENCE OF DENTAL CARIES AND ORAL CANDIDIASIS
1.8.7.3. ARTHRITIS (MOST COMMONLY RHEUMATOID ARTHRITIS)
1.8.8. POPLITEAL (BAKER’S) CYSTS FORM FROM AN OUTPOUCHING OF THE SYNOVIAL SAC INTO THE JOINT SPACE POSTERIOR TO THE KNEE DUE TO THE INCREASED INTRA-ARTICULAR PRESSURE ASSOCIATED WITH RHEUMATOID ARTHRITIS
2. SKELETAL PATHOLOGY
2.1. GOUT
2.1.1. GOUT:
2.1.1.1. BUILDUP OF URIC ACID (MOST COMMONLY CAUSED BY UNDEREXCRETION OF URIC ACID)
2.1.1.1.1. → CRYSTALS OF MONOSODIUM URATE ARE DEPOSITED IN THE ARTICULAR CARTILAGE OF JOINTS, TENDONS AND SURROUNDING TISSUES
2.1.2. ACUTE GOUT:
2.1.2.1. S/SX:
2.1.2.1.1. EXCRUCIATING, SUDDEN, UNEXPECTED, BURNING PAIN, AS WELL AS SWELLING, REDNESS, WARMTH, AND STIFFNESS IN THE AFFECTED JOINT
2.1.2.1.2. MILD FEVER; TACHYCARDIA, BUT ONLY AS A TRANSIENT SYMPATHETIC RESPONSE TO THE EXCRUCIATING PAIN OF AN ACUTE ATTACK
2.1.2.1.3. ACUTE GOUT MOST COMMONLY INVOLVES THE 1ST MTP (METATARSOPHALANGEAL) JOINT—PODAGRA = GOUTY ARTHRITIS OF THE 1ST MTP
2.1.2.1.4. THE EXTENSOR TENOSYNOVIUM ON THE DORSUM OF THE MIDFOOT IS ALSO COMMONLY AFFECTED DURING AN ACUTE GOUTY ATTACK
2.1.3. CHRONIC GOUT:
2.1.3.1. IF GOUT IS POORLY CONTROLLED, MONOSODIUM URATE CRYSTALS MAY DEPOSIT IN PERIARTICULAR SOFT TISSUES
2.1.3.1.1. → TOPHI: GRANULOMAS WITH MULTINUCLEATED GIANT CELLS AND NEGATIVELY BIREFRINGENT MONOSODIUM URATE CRYSTALS (YELLOW WHEN PARALLEL TO THE SLOW RAY)
2.1.3.2. BRISK GRANULOMATOUS REACTION WITHIN TOPHI CAN DESTROY BONE
2.1.3.2.1. → EROSIVE ARTHRITIS
2.1.3.3. TOPHI MAY FORM AROUND JOINTS, BUT ARE ALSO COMMONLY FOUND IN EARLOBES, ACHILLES TENDONS, AND OLECRANON AND PATELLAR BURSAE
2.1.4. PRIMARY GOUT:
2.1.4.1. OVERPRODUCTION OF URIC ACID MAY CAUSE PRIMARY GOUT. FOR EXAMPLE:
2.1.4.2. 1. ALCOHOLISM
2.1.4.2.1. → ↑ TURNOVER OF ADENINE NUCLEOTIDES (IE, ATP) DURING THE CONVERSION OF ACETATE TO ACETYL-COA
2.1.4.3. 2. PROTEIN-RICH DIETS: RED MEAT, SEAFOOD, BEER
2.1.4.4. 3. UNKNOWN ENZYME DEFECTS
2.1.4.5. PRIMARY GOUT MAY ALSO OCCUR SECONDARY TO ↓ EXCRETION OF URIC ACID. FOR EXAMPLE:
2.1.4.5.1. 1. THIAZIDE DIURETICS
2.1.4.5.2. 2. LEAD POISONING
2.1.4.5.3. 3. ALCOHOLISM
2.1.4.6. [NOTE: ALCOHOL CAN CAUSE HYPERURICEMIA BY BOTH INCREASING URATE PRODUCTION AND BY DECREASING URATE EXCRETION, AS DESCRIBE ABOVE]
2.1.5. SECONDARY GOUT (ETIOLOGY OF HYPERURICEMIA IS KNOWN, BUT GOUT IS NOT THE MAIN CLINICAL MANIFESTATION OF THE PERTURBATION/DISEASE):
2.1.5.1. LIKE PRIMARY GOUT, SECONDARY GOUT CAN BE CAUSED BY OVERPRODUCTION OR UNDEREXCRETION OF URIC ACID
2.1.5.2. ↑ NUCLEATED CELL TURNOVER → OVERPRODUCTION OF URIC ACID
2.1.5.2.1. EXAMPLES INCLUDE:
2.1.5.3. INBORN ERRORS OF METABOLISM
2.1.5.3.1. -> OVERPRODUCTION OF URIC ACID, FOR EXAMPLE, LESCH-NYHAN SYNDROME:
2.1.5.4. CHRONIC RENAL DISEASE
2.1.5.4.1. → ↓ EXCRETION OF URIC ACID
2.1.6. ALTHOUGH A BUILD-UP OF URIC ACID IS THOUGHT TO CAUSE GOUT, HYPERURICEMIA IS NOT DIAGNOSTIC
2.1.6.1. WHEN GOUT IS SUSPECTED, THE DIAGNOSIS MUST BE CONFIRMED WITH JOINT ASPIRATION DEMONSTRATING MONOSODIUM URATE CRYSTALS:
2.1.6.1.1. MONOSODIUM URATE CRYSTALS:
2.1.7. TREATMENT:
2.1.7.1. FOR ACUTE ATTACKS, THE GOAL OF TREATMENT IS SIMPLY TO REDUCE PAIN AND INFLAMMATION:
2.1.7.1.1. NSAIDS
2.1.7.1.2. COLCHICINE
2.1.7.1.3. GLUCOCORTICOIDS: IF THERE IS EITHER NO RESPONSE OR POOR TOLERANCE OF NSAIDS AND COLCHICINE, GIVE ORAL PREDNISONE
2.1.7.1.4. INTRA-ARTICULAR STEROID INJECTIONS ARE EFFECTIVE FOR PAIN RELIEF IF ONLY ONE JOINT IS INVOLVED
2.1.7.2. FOR PATIENTS WITH RECURRENT ATTACKS (>1 EPISODE PER YEAR), TREATMENT IS GUIDED BY UNDERLYING PATHOPHYSIOLOGY:
2.1.7.2.1. 1. IF PATIENT IS AN UNDER-EXCRETER OF URIC ACID (24-HOUR URINE URIC ACID LEVEL <600MG)
2.1.7.2.2. 2. IF PATIENT IS AN OVER-PRODUCER OF URIC ACID (24-HOUR URINE URIC ACID LEVEL >600MG)
2.1.7.2.3. NOTE: FEBUXOSTAT IS AN ALTERNATIVE XANTHINE-OXIDASE INHIBITOR TO TREAT CHRONIC HYPERURICEMIA IN PATIENTS WITH INTOLERANCE TO ALLOPURINOL AND/OR RENAL IMPAIRMENT
2.1.7.3. PRECIPITATION OF CALCIUM PYROPHOSPHATE DIHYDRATE CRYSTALS IN CONNECTIVE TISSUES
2.1.7.3.1. → PSEUDOGOUT