case of connective tissue disease

1. CLINICAL MEET
21/12/2013
CASE OF
DySPNEA
DR. GANESH SATPUTE
JR III
DR. D.R. MHASDE UNIT

2. Case History
45 year female, R/o Nana peth, Pune
Came with
c/o Progressive breathlessness since last 6 months
c/o Swelling over both lower limbs since 1 month
Breathlessness gradually increased from NYHA GRADE I to
GRADE IV. It was more on recumbent position.
H/o orthopnea +
H/o joint pains on and off in past,
H/o myalgia and body ache.

3. No h/o chest pain, palpitations
cough with expectoration
fever, rash or oral ulceration
decreased urine output.
swelling of joints or joint stiffness.
• Past history:
No h/o Tuberculosis, DM, HTN, COPD in past.
No history s/o rheumatic fever in childhood.

4. • Family history:
No h/o similar illness in family, no h/o Koch's contact.
• Personal history:
No any addictions, Sleep-disturbed
• Menstrual history:
H/o menopause at the age of 40 yrs.
No postmenopausal bleeding.

5. • GENERAL EXAMINATION:
Afebrile
P- 96/min irregular, all peripheral pulses well felt
No radiofemoral delay.
BP- 130/80mm Hg
Pallor +
Pedal edema + pitting type
No icterus/clubbing /cyanosis/lymphadenopathy.
JVP- Raised.
Raised hard nontender nodules with ulceration discharging
whitish granular discharge from it present over palms ,
soles and digits.

6. • SYSTEMIC EXAMINATION
• CVS:
Inspection: Precordium normal.
Apical impulse seen Lt 5th ICS In Ant. axillary line.
Palpation: Apex beat felt in Lt 5th ICS in Ant. axillary line.
Left parasternal heave+
Asculatation: S1 audible, P2 loud
PSM + in TA.
ESM+ in PA

7. • RS: B/I crepts + in IMA, IAA, ISA
B/l scattered inspiratory ronchi heard all over chest.
• P/A: Soft ,nontender.
Liver 2 cm palpable, nonpulsatile, No splenomegaly.
• CNS: No signifiacant abnormality.

8. DIFFERENTIALS ?

10. Investigations….
24/9 25/9 27/9
Hb
TLC
8.9
PLT
25/9
10.2
9.4
225
HCT
Creat
0.9
SGOT
65
45
31
33
ALP
144
147
0.9
Urea
28
40
30
Na
136
134
137
K
3.5
3.3
4.2
101
Bilirubin
0.8
0.7
-
46
Total
proteins
5.9
ESR
1.2
3.4
BSL
91
Uric Acid
3.6
Albumin
4.6
-
Globulin
1.4.
-
HIV
NEG.
FE
90
-
TIBC
360
-
LDH
220
-
HbsAg
PBS-Predominantly Normocytic,
normochromic.
TLC- 8,000. N75, L23,M1, E1,
Platelets adequate.
NEG.
3.8
25/9
Phosphorus
54
MCV
Calcium
24/9
SGPT
8.6
24/9
Urine analysis : NAD

11. X-rays….

12. ECG….

13. Hand X-rays….

14. X-ray skull….

15. Further workup….
2D Echo : Global hyokinesia, LVEF 35%
Dilated RA and RV
Severe TR
Dilated pulmonary artery ( 35mm)
Moderate pulmonary hypertension
Minimal pericardial effusion.
• USG abdomen: RK 9.3 X 3.2 cms. LK 9.2 X 4.2 cms.
CMD-Good
• OGD Scopy: WNL
• ANA , RA Factor, CRP, ASO sent

16. • Skin opinion:
Imp: ? Tophaceous gout.
? Calcinosis cutis.
Adv: Surgical Biopsy & HPE.
• Biopsy of nodules sent.
• HRCT done.

17. HRCT Chest….

22. Further workup ….
• RA Factor: Negative
• ASO: Negative
• PTH : 45 pg/ml (10-60 pg/ml)
• TFT’s: WNL
ANA : Strongly POSITIVE (2.93)
• ANA blot sent.

23. Biopsy .….

24. ANA Blot….
ANA BLOT
U1RNP
STRONG
POSITIVE
SM
NEGATIVE
SS-A
0.8
RO-52
+ Borderline
SS-B
+ Borderline
Scl-70
NEGATIVE
PM-Scl
NEGATIVE
JO-1
NEGATIVE
Ds DNA
NEGATIVE
Nucleosome
NEGATIVE
Histone
NEGATIVE
Total CPK: 900 IU/L

25. Final diagnosis….
Case of Mixed connective tissue disease with
ILD with severe Pulmonary hypertension
with Corpulmonale with Calcinosis cutis

26. DISCUSSION…. MCTD..
• Overlap syndrome consisting of SLE, systemic
sclerosis, RA, and polymyositis
• These overlap features seldom occur concurrently
• “The crux of the MCTD diagnosis is the presence of
high titers of antibodies to U1-RNP”
• The first clue to diagnosing MCTD is usually a positive
ANA with a high titer speckled pattern.
• Four different diagnostic criteria have been proposed
–
–
–
–
Sharp
Kasukawa
Alarcon-Segovia
Kahn

27. Diagnosis….Sharp’s criterias
Major Criterias
Minor Criterias
Myositis
Pulmonary Involvement
Reynaud's phenomenon
or esophageal dysmotility
Swollen hands or
sclerodactyly
High anti-U1-RNP with
negative anti-Sm
Definite – 4 major (including serology)
Probable – 3 major or 2 major (1st 3
listed) and 2 minor; and serology
Alopecia
Leucopenia
Anemia
Thrombocytopenia
Pleuritis
Pericarditis
Arthritis
Trigeminal Neuralgia
Malar Rash

28. Clinical Presentation…..
• Early Clinical
Findings
 Malaise, easy
fatigability
 Arthralgias
 Myalgias
 Reynaud's
phenomenon
 Low-grade fevers
Unusual
Presentations
FUO
Serositis
Trigeminal
neuropathy
Severe polymyositis
Acute arthritis
Aseptic meningitis
Digital gangrene

29. Pulmonary Manifestations….
• Pleural Effusions
The most discriminatory
• Pulmonary Hypertension
lung function test is DLCO.
• Pleuritic Pain
• Interstitial Lung Disease (30-
50%)
High-resolution CT is
the most sensitive test to
determine the presence
of ILD in MCTD.
• Thromboembolic Disease
The major cause of
• Obstructive Disease
death in MCTD is
• Pulmonary Vasculitis
Pulmonary Hypertension

30. Pericardial Disease….
 Pericardial Involvement
 Scleroderma 59%
 SLE
44%
 RA
24%
 MCTD
30%
ECG : abnormal in
20 % of cases .
RVH, Intraventricular
conduction defects.
 MCTD
 At autopsy – 56% had pericardial disease
 Asymptomatic pericardial effusion – 24-38%

31. Renal involvement….
• 25% of cases
• Glomerulonephritis, nephrotic syndrome, scleroderma renal
crisis, amyloidosis and renal infarcts
• High titer of anti-U1RNP are relatively protective against the
development diffuse proliferative GN.
• When pt do develop renal change,they usually develop
membranous GN

32. Other systems…
GASTROINTESTINAL
Occurring in 60-80
% of patient
Gastroesophageal
reflux, dyspepsia,
dysphagia.
Autoimmune
hepatitis
JOINTS
Arthritis
(Polyarticular)
Juxtraarticular
osteopenia,erosive
arthritis, digital tuft
resorption
HAEMATOLOGY
Anemia of chronic disease,
Thrombocytopenia,
autoimmune hemolytic anemia.
RF: Positive in 50% of patients.
CNS
Trigeminal
neuropathy(MC),
Headache
Angiographic study
reported a high
prevalence of
medium-size vessel
occlusion.

33. Laboratory Findings….
 High titre, speckled ANA pattern
 Leucopenia, anemia, thrombocytopenia
 Elevated ESR
 High titre U1 RNP antibody.
 Complement levels usually normal or high
 Rheumatoid Factor positive in 70% of patients
 Negative findings include anti-dsDNA and anti-Sm antibodies
(if positive, it may represents exclusion criteria for MCTD)

34. Antibody Findings……
Disease
ANA
RF
dsDNA
Sm
Scl-70
RNP
SLE
95-99
20
50-70
30
0
30-50
RA
15-35
85
<5
0
0
10
Diffuse
SSc
MCTD
>90
30
0
0
40
30
95-99
50
00
<5
0
100

35. Management ….
 Immunosuppressants
Corticosteroids and cytotoxic agents, most often
cyclophosphamide, are the most frequently used.
 Recommendation for management are based on
conventional treatment for SLE, PM,DM,RA and Scl
 Drug therapy:CCBs
Prostaglandins