Seronegative Spondyloarthropathies and Systemic Sclerosis

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Seronegative Spondyloarthropathies and Systemic
Sclerosis

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

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• HLA stands for Human Leukocyte Antigen
• this is a genetic region designated because these
  antigens were first detected on peripheral blood
  lymphocytes
• Includes HLA-A,B,C,DR each with many alleles
• Located on chromosome 6

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• HLA
• complex has been associated with a variety of
  diseases
• AS B27
• RA DR4
• SLE DR3
• Reiter's B27

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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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Causes

• The cause of limited scleroderma is yet to be
  determined. Studies of genetic factors show only
  rare occasions of multicase families. Human
  leukocyte antigen associations are present but
  are not strong.
• Autoimmunity,fibroblast dysregulation, have been
  implicated.

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Causes

• The predominance of cases occurring in women
  after their childbearing years and the similar
  clinical presentation of scleroderma to
  graft-versus-host disease has suggested the
  importance of fetal/maternal etiology of
  scleroderma. The possibility of fetal lymphocytes
  retained in the maternal circulation

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Causes

• Environmental factors also are likely important.
  Some similarities in clinical presentation occur
  with silica, L-tryptophan (eosinophilia-myalgia
  syndrome) an over the counter remedy for insomnia
  and premenstrual symptoms.

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Systemic Sclerosis

• In diffuse scleroderma - tendon friction rubs
  (especially over the wrist, ankles and knees)
• In general, patients with CREST syndrome have
  better outcomes than those with diffuse disease
  (patients w/limited disease rarely develop renal
  failure or interstitial lung disease)

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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

• Most frequently first sign in cutaneous features
  (visceral involvement may precede)
• 90 of patients early manifestations -
  polyarthralgia and Raynauds phenomenon
• Subcutaneous edema, fever and malaise common
  symptoms

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Systemic Sclerosis- symptoms/signs

• Skin becomes thickened with loss of normal folds
• Telangiectasia, pigmentation and depigmentation
• ulceration of the fingertips, subcutaneous
  calcification
• dysphagia due to esophageal dismotility

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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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Sclerodermalike disorders
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Systemic Sclerosis-Diagnosis

• Eosinophilic fascitis - rare disorder that
  presents with skin changes resembling diffuse
  systemic sclerosis
• inflammatory abnormalities limited to the fascia
  rather than the dermis and epidermis
• presence of peripheral blood eosinophilia
• absence of Raynauds phenomenon
• good response to prednisone
• have increased risk of aplastic anemia

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Systemic Sclerosis-Diagnosis

• Eosinophilia-myalgia syndrome
• first noted in patients that ingested tryptophan
  (essential amino acid- was sold over the counter
  until banned by FDA)
• weeks-months after ingesting symptoms appeared
• syndrome of severe generalized myalgias,
  cutaneous abnormalities, pulmonary symptoms,
  fever, myopathy, lymphadenopathy
• Patients presenting with systemic sclerosis or
  eosinophilic fascitis-like syndrome should be
  asked about tryptophan use

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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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Systemic Sclerosis- Outcome

• Cases that do not develop severe internal organ
  involvement in the first 3 years do better with
  72 surviving at least 9 years
• 40 - 9 year survival rate in scleroderma

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Systemic Sclerosis- Outcome

• prognosis worse in diffuse scleroderma cases, in
  blacks, in males, and in older patients
• In most cases death results from renal, cardiac
  or pulmonary failure
• Patients may be at increased risk of breast and
  lung cancer

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Systemic Sclerosis- Outcome

• Limited disease is associated with better
  survival rates than diffuse disease (50 at 12 y
  compared to 15 for diffuse scleroderma).

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Systemic Sclerosis- Outcome

• Renal involvement was responsible for one half of
  scleroderma-related deaths in patients with
  widespread skin changes, while patients with
  sclerodactyly alone did not tend to have renal
  disease at all.

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Systemic Sclerosis- Outcome

• Mortality in patients with limited skin
  involvement is a result of cardiac, pulmonary,
  and GI causes.

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Questions ??