Seronegative Spondyloarthropathies and Connective Tissue Disease

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Seronegative Spondyloarthropathies and Connective
Tissue Disease

• Victor Politi, M.D., FACP
• Medical Director, SVCMC, School of Allied Health,
  Physician Assistant Program

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Connective tissue disease

• A connective tissue disease is any disease that
  has the connective tissues of the body as a
  primary target of pathology.
• Many connective tissue diseases feature abnormal
  immune system activity with inflammation in
  tissues as a result of an immune system that is
  directed against one's own body tissues
  (autoimmunity).

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Connective tissue disease

• Diseases in which inflammation or weakness of
  collagen tends to occur are also referred to as
  collagen diseases.
• Collagen vascular disease is a somewhat
  antiquated term used to describe diseases of the
  connective tissues that typically include
  diseases which can be (but are not necessarily)
  associated with blood vessel abnormalities.

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Heritable Connective Tissue Disorders

• Marfan Syndrome - a genetic disease causing
  abnormal fibrillin.
• Epidermolysis bullosa (EB). With these disorders,
  the skin blisters when it is stressed. For
  example, a hug could cause a blister.
• Ehlers-Danlos syndrome - causes progressive
  deterioration of collagens, with different EDS
  types affecting different sites in the body, such
  as joints, heart valves, organ walls, arterial
  walls
• Osteogenesis imperfecta (brittle bone disease) -
  caused by insufficient production of good quality
  collagen to produce healthy, strong bones.

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Marfan Syndrome

• A hereditary disorder of connective tissue
  characterized by tall stature, elongated
  extremities, subluxation of the lens, dilatation
  of the ascending aorta, and "pigeon breast." It
  is inherited as an autosomal dominant trait.

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Marfan Syndrome

• Initial diagnosis is made on the basis of a
  careful examination of the three main affected
  areas the heart, skeleton and eyes.

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Ehlers-Danlos syndrome (EDS)

• Ehlers-Danlos syndrome (EDS) is a heterogeneous
  group of heritable connective tissue disorders
  characterized by articular hypermobility, skin
  extensibility and tissue fragility.
• At this time, research statistics of EDS show the
  prevalence as 1 in 5,000. It is known to affect
  both males and females of all racial and ethnic
  backgrounds.

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Ehlers-Danlos syndrome (EDS)

• Clinical manifestations of EDS are most often
  joint and skin related and may include
• Joints joint hypermobility loose/unstable
  joints which are prone to frequent dislocations
  and/or subluxations joint pain hyperextensible
  joints early onset of osteoarthritis.
• Skin soft velvetlike skin variable skin
  hyper-extensibility fragile skin that tears or
  bruises easily severe scarring slow and poor
  wound healing development of molluscoid pseudo
  tumors .

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SLE

• Inflammation of the connective tissues.
• characterized by antinuclear antibodies and
  multiorgan involvement.
• Peak incidence of systemic lupus erythematosus is
  in people aged 15-40 years, with a female-to-male
  ratio of at least 51.
• It is up to 9x more common in women than men.

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SLE

• The criteria include malar rash, discoid rash,
  photosensitivity, oral ulcers, arthritis,
  serositis, renal disorder, neurologic disorder,
  hematologic disorder, immunologic disorder, and
  positive ANA.

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Rheumatoid Arthritis

• Rheumatoid arthritis is a chronic inflammatory
  systemic disease primarily characterized by
  diarthrodial joint involvement.
• The prevalence of rheumatoid arthritis increases
  with age and has a peak incidence in persons aged
  40-60 years, with a female-to-male ratio of 31.

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RH
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Rheumatoid Arthritis

• The criteria include morning stiffness for at
  least 1 hour, arthritis of 3 or more joint areas,
  arthritis of the hands, symmetric arthritis,
  rheumatoid nodules, serum RF, and radiographic
  changes.
• RF is found in the serum of approximately 85 of
  patients with rheumatoid arthritis.

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Scleroderma

• Scleroderma is an activation of immune cells
  which produces scar tissue in the skin, internal
  organs, and small blood vessels.
• It affects women 3x more often than men overall,
  but increases to a rate 15 x gt for women during
  childbearing years.

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Sjögren's syndrome

• A chronic, slowly progressing inability to
  secrete saliva and tears.
• It can occur alone or with rheumatoid arthritis,
  scleroderma, or systemic lupus erythematosus.
• Nine out of 10 cases occur in women, most often
  at or around mid-life.

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Sjögrens syndrome

• The classic clinical presentation for Sjögren
  syndrome is the combination of dry eyes
  (keratoconjunctiva sicca) and dry mouth
  (xerostomia).
• The criteria for diagnosis of primary Sjögren
  syndrome include symptoms and objective signs of
  ocular dryness, symptoms and objective signs of
  dry mouth, and serologic evidence of a systemic
  autoimmunity by the presence of RF, ANA, or
  antibodies to SSA (Ro) or SSB (La).

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Sjögrens syndrome

• Primary Sjögren syndrome may involve multiple
  organs other than the eyes and mouth.
• Secondary Sjögren syndrome occurs when the
  symptoms and signs of Sjögren syndrome are
  present with another connective-tissue disease
  and most frequently with rheumatoid arthritis.

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Polymyositis/dermatomyositis

• The diagnosis is uncommon, with an incidence
  range from 2-10 cases per million.
• A bimodal age distribution exists, with peaks at
  ages 10-15 years and at ages 45-60 years
• The overall female-to-male ratio is 31.

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Polymyositis/dermatomyositis

• The 5 possible criteria for diagnosis are
  symmetrical weakness, elevation of muscle
  enzymes, electromyographic evidence, muscle
  biopsy evidence, and dermatologic features.
• A definite diagnosis of polymyositis must include
  4 criteria without a rash.
• The diagnosis of dermatomyositis is made when 3
  criteria are present plus the rash.

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Reactive Arthritis

• HLA-B27 positive (50-80 of cases)
• Formerly called Reiters Syndrome
• Tetrad of urethritis,conjunctivitis/uveitis,mucocu
  taneous lesions (mouth ulcers) and aseptic
  arthritis (oligoarthritis)
• Most common in young men
• Often follows infection

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Reactive Arthritis

• Most cases develop days - weeks following
  dysenteric infection (shigella, salmonella,
  yersinia, Campylobacter) or sexually transmitted
  disease (chlamydia trachomatis or Ureaplasma
  urealyticum)
• To be distinguished from GC arthritis(migratory
  polyarthralgias) and non GC acute bacterial
  (septic) arthritis ie staph.

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Reactive Arthritis

• Arthritis - usually asymmetric - involving large
  weight bearing joints (knees, ankle)
• In 20 of cases - sacroiliitis or ankylosing
  spondylitis present
• systemic symptoms - fever weight loss common at
  initial stage of disease
• Other symptoms -
• mucocutaneous lesions
• carditis aortic regurgitation may occur

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Reactive Arthritis

• Most signs of the disease disappear within days
  to weeks
• arthritis symptoms however may persist for months
  or years
• common for recurrences - can involve any
  combination of clinical manifestations - can be
  followed by permanent sequelae (joints)

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Reactive Arthritis- differential dx

• Gonococcal arthritis can mimic reactive arthritis
• however, in gonococcal arthritis
• marked improvement 24-48 hrs after antibiotics
• culture results distinguish two disorders
• also must consider rheumatoid arthritis,
  ankylosing spondylitis and psoriatic arthritis
• no association between HIV and reactive arthritis

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Reactive Arthritis - Tx

• NSAIDs
• tetracycline's
• sulfasalazine
• Anti-TNF agents (etanercept, infliximab)

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Psoriatic Arthritis

• In 15-20 of psoriasis patients arthritis
  coexists
• There are several subsets of arthritis that may
  accompany psoriasis
• joint disease resembles RA, polyarthritis -
  symmetric, fewer joints involved than in RA
• oligoarticular form - considerable destruction of
  affected joints

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Psoriatic Arthritis

• disease pattern where distal interphalangeal
  joints primarily affected ,pitting of nails,
  onycholysis frequent
• arthritis mutilans (severe deforming- with marked
  osteolysis) pencil in cup deformity
• spondylitic form (primary involvement -
  sacroiliitis, spinal involvement) 50 of cases
  HLA-B27 positive

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Psoriatic Arthritis

• Psoriasis usually precedes arthritis in 80
• 20 of cases it occurs simultaneously
• patient may have a single patch of psoriasis and
  unaware of its connection to arthritis
• psoriasis may not be present at time of exam
  (important to obtain personal history)

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Psoriatic Arthritis- Radiographic findings

• Help distinguish it from other forms of arthritis
• marginal erosions of bone
• irregular destruction of joint and bone
• phalanx may appear - sharpened pencil
• paravertebral ossification
• fluffy periosteal new bone -
• _at_ insertion of muscles and ligaments into bone,
  shafts of metacarpals, metatarsals and phalanges

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Psoriatic Arthritis- Treatment

• Symptomatic
• NSAIDs
• methotrexate
• PUVA therapy for skin lesions
• Corticosteroids (less effective in psoriatic
  arthritis may exacerbate psoriasis)
• antimalarials may also exacerbate psoriasis

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Arthritis with GI symptoms

• 1/5 of patients with inflammatory bowel disease
  have arthritis
• 2/3 of patients with Whipples disease have
  arthralgia or arthritis (usually episodic/large
  joint polyarthritis) Arthritis usually precedes
  Whipples by years (fever,lymphadenopathy,arthralg
  ias,malabsorption ,infection w/tropheryma
  whippelii.)

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Arthritis with GI symptoms

• Two forms of arthritis are seen in Crohns
  disease and ulcerative colitis
• peripheral arthritis (non deforming asymmetric
  oligoarthritis of large joints)
• spondylitis (indistinguishable by symptoms or
  x-ray from ankylosing spondylitis)50 of cases
  are HLA-B27-positive

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• In most cases arthritis improves with controlling
  intestinal inflammation.

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Systemic Sclerosis

• Chronic disorder characterized by diffuse
  fibrosis/thickening of skin ,telangiectasia and
  pigmentation changes
• Cause unknown
• 3rd - 5th decade onset
• Women affected
• 2 - 3 times more frequently than men

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Systemic Sclerosis

• Two Forms
• limited (80 of cases) CREST syndrome -
  scleroderma limited to face and hands
• diffuse (20 of cases) trunk and proximal
  extremities also affected

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CREST Syndrome
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Scleroderma
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CREST Syndrome

• Calcinosis
• In scleroderma, calcific deposits are found
  predominantly in the extremities, around joints,
  and around bony prominences.
• Deposits typically are found in the flexor
  surfaces of the hands and the extensor surfaces
  of the forearms and knees.
• The deposits rest in the dermis but can be found
  in deeper periarticular tissues.

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CREST Syndrome

• Raynaud phenomenon
• Triphasic color changes of pallor, cyanosis, and
  erythema represent phases of vasoconstriction,
  slow blood flow, and reperfusion, respectively.
• Color changes extend proximally from the tips of
  digits to various levels, with a well-demarcated
  border.

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CREST Syndrome

• Esophageal dysmotility
• The earliest change in the distal esophagus
  (primarily smooth muscle) is an uncoordinated
  disorganized pattern of contractions resulting in
  low amplitude or absent peristalsis.
• Lower esophageal sphincter (LES) pressure
  typically is lower than in healthy controls, and
  incomplete relaxation of the LES occurs,
  according to Sjögren.

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CREST Syndrome

• Sclerodactyly
• The process typically begins in the distal
  fingers and advances proximally.
• The process also may occur on the face, over the
  forehead, and around the mouth. Facial
  involvement can lead to a mauskopf (mouse head)
  appearance. Lips become thinner, and radial
  furrowing develops around the mouth. The oral
  aperture is reduced in size (microstomia).
  Wrinkles over the forehead diminish.

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CREST Syndrome

• Telangiectases are flat and nonpulsatile and
  typically have a rectangular or elongated shape.
  The vessels are so close together that they
  appear as discrete mats.

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Systemic Sclerosis- symptoms/signs

• Diffuse pulmonary fibrosis
• GI tract symptoms caused by fibrosis and atrophy
• hypomotility
• malabsorption from bacterial overgrowth
• diverticular develop

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Systemic Sclerosis- symptoms/signs

• Renal crisis (usually indicative of poor
  prognosis - though many cases treated
  successfully w/angiotensin-converting enzyme
  inhibitors)
• Cardiac symptoms
• pericarditis
• heart block
• myocardial fibrosis
• right heart failure secondary to pulmonary HTN

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Systemic Sclerosis- Lab findings

• Mild anemia often present
• Antinuclear antibody tests - positive
• Scleroderma antibody (SCL-70) directed against
  topoisomerase III
• 1/3 of patients w/diffuse systemic sclerosis
• 20 of patients w/CREST syndrome (anticentromere
  ab seen in 50 crest but 1 of syst. Scler.

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Systemic Sclerosis - Treatment

• Symptomatic and supportive
• Intervention for management of specific organ
  manifestations (ie., Raynaud's syndrome - calcium
  channel blockers, esophageal disease - H2
  blockers, etc.)

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Questions ??