Seronegative Spondyloarthropathies and

Systemic Sclerosis

Victor Politi, M.D., FACPMedical Director, SVCMC, School of Allied

Health, Physician Assistant Program

• 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

• HLA• complex has been associated with a variety

of diseases• AS B27• RA DR4• SLE DR3• Reiter's B27

Reactive Arthritis

• HLA-B27 positive (50-80% of cases)• Formerly called Reiter’s Syndrome• Tetrad of

urethritis,conjunctivitis/uveitis,mucocutaneous lesions (mouth ulcers) and aseptic arthritis (oligoarthritis)

• Most common in young men• Often follows infection

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.

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

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)

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

Reactive Arthritis - Tx

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

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

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

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)

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 -

• @ insertion of muscles and ligaments into bone, shafts of metacarpals, metatarsals and phalanges

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

Arthritis with GI symptoms

• 1/5 of patients with inflammatory bowel disease have arthritis

• 2/3 of patients with Whipple’s disease have arthralgia or arthritis (usually episodic/large joint polyarthritis) Arthritis usually precedes Whipple’s by years (fever,lymphadenopathy,arthralgias,malabsorption ,infection w/tropheryma whippelii.)

Arthritis with GI symptoms

• Two forms of arthritis are seen in Crohn’s 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

• In most cases arthritis improves with controlling intestinal inflammation.

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

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

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.

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

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.

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)

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.

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.

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.

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.

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.

Systemic Sclerosis- symptoms/signs

• Most frequently first sign in cutaneous features (visceral involvement may precede)

• 90% of patients early manifestations - polyarthralgia and Raynaud’s phenomenon

• Subcutaneous edema, fever and malaise common symptoms

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

Systemic Sclerosis- symptoms/signs

• Diffuse pulmonary fibrosis• GI tract symptoms caused by fibrosis and

atrophy– hypomotility– malabsorption from bacterial overgrowth– diverticular develop

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

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.

Sclerodermalike disordersDiffuse sclerodermaLimited sclerodermaMixed connective tissuediseaseVinyl chloride diseaseSilica exposureEosinophilic fasciitisEosinophilia-myalgiasyndromeToxic oil syndromeInsulin-dependent diabetesmellitusCarcinoid syndromeMyeloma

ParaproteinemiaScleromyxedemaChronic graft-versus-hostdiseasePOEMS syndrome(polyneuropathy, organomegaly,endocrinopathy, M protein, skin changes)Porphyria cutanea tardaPhenylketonuria

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 Raynaud’s phenomenon– good response to prednisone– have increased risk of aplastic anemia

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

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.)

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

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

Systemic Sclerosis- Outcome

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

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.

Systemic Sclerosis- Outcome

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

Questions ??