Systemic sclerosis (SSc) is a chronic multisystem disease
characterized by microangiopathy, fibrosis of the skin and internal organs, and
autoimmune disturbances. Although it is
a chronic disease, scleroderma can present to emergency with symptoms unless
treated aggressively can result in death of the patient.
ACUTE SCLERODERMA RENAL CRISIS (SRC )
Scleroderma renal crisis develops in
approximately 10% – 15% of patients.(1)It is characterized by:
Acute onset of renal
Abrupt onset of moderate to marked hypertension (although some
patients remain normotensive)(2)
A urine sediment that is usually normal or reveals only mild
proteinuria with few cells or casts
also characterized by microangiopathic haemolytic anemia and thrombocytopenia.
Congestive heart failure and pericardial effusions are common.(3)
Approximately 80% of the renal crisis occur
in patients with diffuse cutaneous systemic sclerosis within the first 4-5
years of disease. Other risk factors include high dose steroids and presence of anti-RNA polymerase III antibody.
treatment of choice for scleroderma renal crisis is therapy with ACE
inhibitors.ACE inhibitors are of value even in normotensive renal crisis. Even
in patients on dialytic support, continuation of ACE inhibitors often leads to
enough renal recovery to permit dialysis discontinuation after 6-18 months.
Aggressive treatment of hypertension can stabilize or even
improve renal function in up to 55% to 70% of cases, if begun before marked
irreversible vascular injury has occurred.(3) Nevertheless, the
mortality is high and a poor outcome is common.(4) Patients who fail
to respond to ACE inhibitor may still respond to potent vasodilators such as
minoxidil along with beta blockers and diuretics. Patients with
severe scleroderma renal crisis have a component of myocarditis and ventricular
stiffness. Hence maintenance of blood volume is essential.
The improvement in renal function can continue for up to 2
years. Allograft survival is lower compared with that of transplant recipients
thrombocytopenic purpura (TTP), is a rare but potentially lethal condition. 5
The diagnosis is made clinically and is classically characterized by a pentad
of thrombocytopenia, microangiopathic hemolytic anemia, transient neurological
symptoms, renal dysfunction, and fever.Basic pathogenesis is presence of large
von Willebrand factor(vWF) multimers
ascribed to deficiency of the vWF-cleaving protease (ADAMTS13) enzyme 6.The vWF cleaving protease done by
activity-based assay, will be normal in SRC and ADAMTS13 level will be extremely low in TTP.
The heart is one
of the major organs involved in scleroderma. Cardiac involvement can
generally be divided into direct myocardial effects and the indirect effect of
other organ involvement . Direct myocardial disease includes myocarditis,
cardiac failure, cardiac fibrosis, coronary artery disease, conduction system
abnormalities, and pericardial disease.
RIGHT HEART FAILURE AND PAH
failure is most commonly the result of pulmonary hypertension. Pulmonary
hypertension is a common manifestation of scleroderma and a poor prognostic
PAH results from restricted flow through the
pulmonary arterial circulation leading to increased pulmonary vascular
resistance and right heart failure.
PAH in the
context of pulmonary fibrosis is of
moderate degree and has slow progression.PAH
occurs due to increase in resistance in pulmonary vasculature.PAH in SSc
patients with minimal or no pulmonary fibrosis is a severe complication, and is
the result of narrowing of small pulmonary arteries.
of PAH include dyspnea on exertion, fatigue, chest pain, dizziness,
palpitations, and edema at the lower extremities. On examination, a loud
pulmonary component of the second heart sound, gallop, and pansystolic murmur
of tricuspid regurgitation may be found, along with features of right heart
failure in advanced cases7.
Chest X-ray and
electrocardiogram may reveal signs suggestive of PAH, mainly in the later
stages, such as an enlarged pulmonary artery, attenuation of peripheral
pulmonary vascular markings (at the chest X-ray), and peaked P wave ? 2.5 mm in
leads II, III and Avf7,8. If PAH is suspected, a transthoracic
Doppler echocardiography is recommended.7,8 On echocardiography, PAH
is defined as mean PAP > 25 mmHg at rest, > 30 mmHg during exercise, or
systolic pulmonary pressure > 40 mmHg. Clues to diagnosis of PAH can be an
elevated tricuspid regurgitation velocity jet above 2.8 m/s, or a dilated right
ventricle or atrium9. Reduced
carbon monoxide diffusing capacity is a marker of pulmonary vascular disease
and is standardly used in the diagnostic approach when PAH is suspected. Of
note, it is associated with poor prognosis.
the treatment,all patients suspected to
have PAH after noninvasive evaluation should undergo right heart catheterization.
This method is the gold standard for diagnosing PAH, and allows for the
measurement of the transpulmonary gradient (PAP mean wedge).It was found to be significantly elevated only in
PAH patients, but not in patients whose pulmonary hypertension was due to
increased cardiac output, left heart myocardial or valvular disease8,10.
A more reliable diagnostic parameter for PAH is pulmonary vascular resistance ,
which reflects the influence of transpulmonary gradient and cardiac output and
is only elevated if the vascular obstruction occurs within the precapillary
pulmonary circulation. However, PVR can also be elevated in patients with valve
disease or left ventricular heart disease26. Consequently, PAH is a
diagnosis of exclusion. In the absence of lung disease, thromboembolism, left
ventricular or valve pathology, the diagnosis of PAH requires both a mean PAP
greater than 25 mmHg and a PVR greater than 3 Wood units with a pulmonary
capillary wedge pressure