3. MCTD
 A autoimmune disease with overlapping features of
SLE, systemic sclerosis and polymyositis, and
presence of the antibody that reacts with U1-
ribonucleoprotein (RNP).
 Diagnostic criteria:- 3 of the followings: synovitis or
myositis (1 must be present), edema of hands,
Raynaud phenomenon, acrosclerosis and serologic
evidence of positive anti-snRNP in atleast moderate
titer.(1)

4. PAH
 Pulmonary arterial hypertension (PAH) is
haemodynamically defined as a resting mean
pulmonary arterial pressure >25mmHg with a normal
pulmonary capillary wedge pressure of <15mmHg on
right heart catheterization.
 Pulmonary hypertension is suggested when an
echocardiogram derived estimate of pulmonary arterial
systolic pressure exceeds 40mm Hg at rest.

6. Pulmonary arterial hypertension
 Sporadic
 Familial
 Related to:
Collagen vascular disease
Congenital systemic-to-pulmonary shunts (large, small, repaired, or
nonrepaired)
Portal hypertension
HIV infection
Drugs and toxins(fenfluramine, amphetamines or cocaine)
Others (glycogen storage disease, Gaucher disease, hereditary
hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative
disorders, splenectomy)
Pulmonary veno-occlusive disease
Pulmonary capillary hemangiomatosis
Pulmonary venous hypertension
 Left-sided atrial or ventricular heart disease
 Left-sided valvular heart disease

7. Pulmonary hypertension associated with hypoxemia
 Chronic obstructive pulmonary disease
 Interstitial lung disease
 Sleep-disordered breathing
 Alveolar hypoventilation disorders
 Long-term exposure to high altitude
PHTN sec to chronic thrombotic or embolic disease
 Thromboembolic obstruction of proximal pulmonary arteries
 Thromboembolic obstruction of distal pulmonary arteries
 Pulmonary embolism (tumor, parasites, foreign material)
Miscellaneous
 Sarcoidosis, histiocytosis X, lymphangiomatosis, compression of
pulmonary vessels (adenopathy, tumor, fibrosing mediastinitis)

8.  MCTD: first described as an apparently distinct
rheumatic disease syndrome in 1972 (2)
 Prevalence : 10/100 000 in U.S (3)
 The female : male ratio is about 9 : 1 (3)
 The lung is a common target organ in 25–85% of
patients with MCTD
 In MCTD the prevalence of pulmonary arterial
hypertension (PAH) is between 20% and 30% (3)

9. Pathogenesis of MCTD
 Unclear etiology
 The expression of intracellular ribonucleoproteins on
the cell surface in apoptotic blebs.
 Immune tolerance breakdown as a result of post-
translational modification of the 70 kDa molecule or as
a result of molecular mimicry with viral antigens.

10. Pathogenesis of PAH
 Impaired smooth muscle Ca channel function.
 Endothelial cell function damage.
 Decreased production of vasodilatating nitrogen
monoxide and prostacyclin.
 Increases the production of vasoconstrictor
thromboxane A2 and endothelin-1 in the endothelial
cells.
 Vasoconstriction, proliferation of small and medium
size arteries, this provoke a predisposition to
thrombosis.

11. Pathology
 Intimal hyperplasia
 Hypertrophic media
 Plexiform lesion
 Microthrombi

12. Narrowing of the pulmonary arteries and arterioles in the lung
specimen

14. Major clinical features of MCTD % involvement
Arthritis/ arthralgia 95
Raynauds 85
Oesophageal involvement 67
Impaired lung diffusion 67
Swollen hands 66
Myositis 63
Scleroderma 33
Serositis 27
Trigeminal neuralgia 25
Renal disease 10
Cerebral involvement 10

15. Signs and Symptoms of PAH
 shortness of breath on exertion
 fatigue
 angina
 syncope and pre-syncope
 abdominal distension
 peripheral edema
 Jugular vein distension
 accentuated pulmonary component of S2
 hepatomegaly and
 ascites.

17.  Myositis
 Fibrosing alveolitis
 Pulmonary hypertension: most common cause of death in
MCTD
The prognosis for MCTD with PAH is extremely poor, and the
mean duration of survival from the onset of the underlying
disease is 4.4 years for these patients. (4)
Median survival in untreated patients is only 12 months, and the
risk of death is nearly tripled. This survival rate is in the range of
some malignant diseases and thus highlights the need for early
diagnosis and treatment. (5)
The tendency of the disease to evolve into one of its sister
diseases such as SLE or systemic sclerosis

19. MCTD
 Anti-U1RNP antibodies (high titers)
 Hematological findings: leukopenia, thrombocytopenia
and a high erythrocyte sedimentation rate.
 High immunoglobulin; esp Ig G
 Complements: N or High
 Rh factor: high
 Exclusion criteria : presence of anti-Sm and anti-DNA
antibodies.

20. PAH
 Transthoracic Doppler echocardiography is the technique of
choice for early evaluation of PAH because it is noninvasive and
allows serial determinations of the mean PAP. It should be
repeated every 1-2 yrs.
 TTE estimates the right ventricular systolic pressure (RVSP),
which is equivalent to the pulmonary artery systolic pressure in
the absence of pulmonary outflow obstruction, by measuring the
systolic regurgitant tricuspid flow velocity.
 TRV jet > 2.5 m/sec with unexplained dysnea or TRV jet > 3
m/sec: indicates the need RHC

21.  While TTE is an excellent screening tool for PAH, it has
limitations:
 RVSP increases with age and body mass index
 RVSP is reported to be 28+/-5mmHg with a range of 15–
57mmHg.
 By assuming a diagnosis of PAH with a RSVP of >40 mmHg, a
number of false positive diagnosis will be made.
 TTE tends to underestimate RVSP in patients with severe PAH
and to overestimate RVSP in patients with normal pressures or
less severe PAH.

22.  Right ventricle catheterization is considered to be the
confirmatory test for PAH diagnosis.
 Right heart cath tells the severity of haemodynamic changes
and test the vasoreactivity of the pulmonary circulation by using
short-acting pulmonary vasodilators
 The high level of anti-U1RNP autoantibodies.
 The presence of the anti-endothelial cell antibodies, the
circulating thrombomodulin and vWFAg may be provoking
factors for the development of PAH associated with MCTD.
 BNP and pro-BNP increases in early disease stages, and
correlate well with haemodynamic measures and survival .

23.  EKG: RAD, RVH
 CXR : prominent pulm artery
 Pulmonary function testing (PFT): to exclude the underlying
airway or parenchymal lung disease.
 A fall in DLCO with normal lung volumes is suggestive of the
early development of pulmonary arterial hypertension
 Every 6-12 months
 6-min walk test: determine disease severity, response to therapy
and progression . Its interpretation is limited in MCTD sec to
associated co-morbidities.
 High-resolution CT for interstitial lung disease and
 V/Q scan for chronic thrombembolic disease.

24. New York Heart Association functional
classification
Class 1 No symptoms with ordinary physical activity.
Class 2 Symptoms with ordinary activity. Slight
limitation of activity.
Class 3 Symptoms with less than ordinary activity.
Marked limitation of activity.
Class 4 Symptoms with any activity or even at rest.

25. World Health Organization functional assessment
classification
Class I Patients with PH but without resulting limitation of physical activity.
Ordinary physical activity does not cause undue dyspnea or
fatigue, chest pain, or near syncope.
Class II Patients with PH resulting in slight limitation of physical activity.
They are comfortable at rest. Ordinary physical activity causes
undue dyspnea or fatigue, chest pain, or near syncope.
Class III Patients with PH resulting in marked limitation of physical activity.
They are comfortable at rest. Less than ordinary activity causes
undue dyspnea or fatigue, chest pain, or near syncope.
Class IV Patients with PH with inability to carry out any physical activity
without symptoms. These patients manifest signs of right-heart
failure. Dyspnea and/or fatigue may even be present at rest.
Discomfort is increased by any physical activity.

27. MCTD
 Non-steroidal anti-inflammatory drugs: 33% cases
 Raynaud’s phenomenon: electrically heated gloves,
CCB like nifedipine.
 Antimalarial agents: hydroxychloroquine.
 Disease-modifying antirheumatic drugs:
sulphasalazine
 Corticosteriods
 Immunosuppressive drugs: cyclophosphamide,
azathioprine and MTX

28. PAH
 Immunization against influenza and pneumococcal
pneumonia is recommended.
 Avoid pregnancy; in severe PAH it is recommend to
terminate of pregnancy.
 Avoid estrogen containing OCP; increase risk on
thromboembolism
 Avoid hot bath: peripheral vasodilation and syncope.
 Laparoscopic procedure with CO2 use for abdominal
insufflation, may cause hypercarbia and pulm
vasoconstriction.

29. high altitude Hypoxemia, pulmonary Avoid altitudes 1800 m
vasoconstriction supplemental oxygen > 91%
Air travel Hypoxemia, pulmonary supplemental oxygen > 91%
vasoconstriction
Heavy exertion Near-syncope, syncope Engage in low-level activity or
cautious, graduated exercise,
such as walking
Bending over and rising Near-syncope, syncope Rise slowly from bending, sitting,
quickly or lying positions
Use of decongestant Vasoconstriction, worsening consider nonsedating
medications pulmonary antihistamines or local
hypertension treatments,
such as nasal steroids
Use of appetite Worsening pulmonary hypertension Have dietary and nutritional,
suppressants or diet pills consultation; engage in cautious
low-level exercise
High sodium intake Fluid retention, right-heart failure Follow 2-g sodium diet
Cigarette smoking Worsening of intrinsic lung disease; Stop smoking (preferably without
Nicotine is a vasoconstrictor use of nicotine replacement
therapy)

30. PAH
 Supplemental oxygen: sats> 90%
 Diuretics are indicated for right ventricular volume overload.
 Digitalis is sometimes used for refractory right ventricular failure
 Anticoagulation with warfarin is recommended in idiopathic
PAH.
 Anticoagulation is controversial for patients who have PAH due
to other causes, such as scleroderma, MCTD or congenital
heart disease.
 NSAIDs and Corticosteroids: improve pulm vascular disease.

31.  Vasodilator Testing and Calcium-Channel Blockers
 Patients who have a substantial response to a short-acting
vasodilator should be considered candidates for treatment with
oral calcium-channel blockers
 Short-acting agents, including intravenous epoprostenol or
adenosine and inhaled nitric oxide.
 Positive response: PAH is a decrease of at least 10 mm Hg in
mean pulmonary arterial pressure to 40 mm Hg or less, with
increased or unchanged cardiac output.
 Agents with negative inotropic effects, such as verapamil,
should be avoided.
 Vasodilator response is present in small number of patients
with CTD

32.  Prostanoids: vasodilator and antiplatelet.
 Improve functional capacity and hemodynamic; with no
demonstrable survival benefit.
Epoprostenol therapy: functional NYHA class III and IV with
idiopathic PAH or PAH due to scleroderma/MCTD, it is generally
reserved for those with advanced disease refractory to oral
therapies. Needs an indwelling central venous catheter.
Treprostinil: S/C; NYHA class II, III, IV & when oral therapy fails.
Iloprost: Inhalation, NYHA III and IV.

33.  Endothelin-Receptor Antagonists
Endothelin-1 is a potent vasoconstrictor and smooth
muscle mitogen.
Bosentan is approved in the United States for patients
with PAH in NYHA class III and IV.
S/E : hepatotoxicity, anemia, teratogenicity, testicular
atrophy.
Response on 6MWD is less in CTD-PAH

34.  Phosphodiesterase-5 Inhibitors
 Drugs that selectively inhibit cGMP-specific
phosphodiesterase augment the pulmonary vascular
response to endogenous or inhaled nitric oxide.
 Sildenafil/Tadalafil has recently been approved by the
U.S. Food and Drug Administration for use in PAH.

35. Combination therapy
 Combining drugs with different targets is
mechanistically appealing because of potential
synergy.
 Sildenafil + intravenous epoprostenol improves
exercise capacity, hemodynamic measurements, time
to clinical worsening, and quality of life. (PACES trail);
mainly in IPAH.
 Sildenafil and bosentan: less efficacy in CTD.

36. Surgical therapy
 Atrial septostomy: as a palliative procedure or as a
stabilizing bridge to lung transplantation.
 Lung transplantation.

37. Follow up
 Clinical symptoms
 P Exam: B.P monitoring, basal rales
 CBC, BMP,CK, UA
 anti-U1-RNP antibodies titers.
 Pulm HTN: screening: CXR, EKG, PFT, ECHO.
 Confirmation: Rt heart cath
 Rarely: Lung biopsy.

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