2. CLINICO-PATHOLOGICAL CONFERENCE BY Medical Unit 1 BBH

3. CLINICAL SCENERIO
A PATIENT WITH COLD SENSITIVITY AND ORBITAL PUFFINESS PRESENTED BY DR AMBER FAYYAZ JAFRI PGT MU I,BBH

6. PERSONAL PROFILE
Name : Alina Age: 23 yrs Gender : Female Marital status: Unmarried Occupation: Nil Residence: Rawalpindi DOA: 9th February MOA: OPD

7. Presenting Complaints
Gen. body aches months
Multiple joint pains months
Fever weeks
Oral ulcers weeks
Periorbital puffiness weeks
Swelling of hands weeks

8. HISTORY OF PRESENTING ILLNESS
Generalized body aches 6 months
Polyarthritis with morning stiffness two months.
Low grade intermittent fever of three weeks .
Periorbital puffiness associated with purplish discoloration of eyelids
Oral ulcers
Raynaud's phenomenon

9. SYSTEMIC INQUIRY Dysphagia Neuropsychiatric symptoms Hematuria
Myalgias
Important negatives
Dysphagia
Neuropsychiatric symptoms
Hematuria
Pleuritic chest pain
Abdominal pain
Skin tightness
Dryness of skin and eyes

10. Family history:- Not significant Past medical and surgical history:- Personal history :- Non smoker, non addict. No known allergies. Menstrual history:- Normal.

11. General Physical Examination
A young lady with following findings.
Digital infarcts
Multiple oral ulcers
Heliotrope rash
Few subcentimeter posterior cervical lymph nodes
Swelling of hands and periorbital puffiness
Vitals
BP : 110/70 mmHg
Pulse : 84/min
Temp : oF
R/R : 20/min

13. Systemic Examination MUSCULOSKELETAL SYSTEM :
There was no visible deformity of the joints
Tenderness and swelling of small joints
No limitation of movements

14. CARDIOVASCULAR SYSTEM
RESPIRATORY SYSTEM
Unremarkable
CARDIOVASCULAR SYSTEM
No signs of pulmonary hypertension

15. GASTROINTESTINAL SYSTEM
Unremarkable
CENTRAL NERVOUS SYSTEM:-
Higher mental functions : intact
Cranial nerves : intact
Sensory and Motor examination: intact
Cerebellar signs : Absent
Gait : normal

16. DIFFERENTIAL DIAGNOSIS
SLE RA
Scleroderma
Dermatomyositis
Mixed connective tissue disorder
Overlap syndrome
Undifferentiated connective tissue disorder

17. INVESTIGATIONS

18. Blood CP TLC : 2.5 (Decreased) RBC : 4.05 Hb: 9.6 g/Dl (Decreased)
MCV : 81.7 FL
Platelet : 100 (Decreased)
ESR : 98(Raised)
CRP: 12 (Raised)

19. Biochemistry Urine R/E , LFT’S, RFT’S : Normal Serum LDH : Normal
Coomb’s test : Negative.

20. ECG
ECG: Normal. No feature of pulmonary arterial hypertension.

21. IMAGING Echocardiography :- Ultrasound abdomen : CXR: Normal
No evidence of pericardial effusion or any valvular abnormality. Ejection fraction 55%. No evidence of hypokinetic walls.

24. Autoimmune profile
RA :+ve
Anti CCP antibodies : +ive

25. Autoimmune profile ANA : +ve Anti ds DNA : -ve
Complement C 3 : 0.2 ( )(Decreased)
Complement C4 : 0.05 ( )(Decreased)

26. Autoimmune profile Anti Smith antibody : -ve Anti SSA (Ro) : +ve
Anti SSB (La) : +ve
Anti Jo 1 antibody : -ve
Anti scl 70 : +ve

27. Muscle enzymes
Aldolase : Raised (19.5u/L)
CPK : Raised (866mcg/L)

28. Autoimmune profile continued
Anti U1 RNP Antibodies: -ve

29. Electromyography Excessive spontaneous activity.
Polyphasic potential of short duration with low amplitude

30. DIAGNOSIS
Based on the history ,examination, laboratory investigations and careful scrutiny of various features present in this patient suggestive of more than one autoimmune disorder .

31. SLE DIAGNOSTIC CRITERIA (2015 ACR)
CLINICAL CRITERIA
OUR PATIENT
Malar rash _
Discoid rash
Photosensitivity
Oral ulcers +
Arthritis
Serositis -
Renal involvement
Neurological involvement
Heamatological involvement
Thrombocytopenia

32. Required 4 out of 11 , our patient 5 out of 11
Leucopenia +
ANA
Anti ds DNA _
Anti Sm
Antiphospholipid antibody
Low complement
Required 4 out of 11 , our patient 5 out of 11

33. 2015 ACR/EULAR DIAGNOSTIC CRITERIA FOR SCLERODERMA
Skin thickening of fingers of both hands extending upto MCP joint(sufficient)/ 9 _
Finger tip lesions(digital ulcers)/2 +
Puffy fingers / 2
Telangectasias/ 2
Abnormal nailfold capillaries/2
PAH/ILD(max score 2)
Raynaud’s phenomenon/3
Anti Scl 70(max score 3)
Required is 9 , our patient has score of 10

34. 2010 ACR/EULAR CRITERIA FOR RA
CRITERION
SCORE
JOINTS AFFECTED
1 Large joint
2-10 large joints 1
1-3 small joints 2
4-10 small joints 3
SEROLOGY
Negative RF or ACPA
Low positive RF or ACPA
High positive RF or ACPA

35. Required score 6 or more, our patient 7.
DURATION OF SYMPTOMS
<6 Weeks
>6 Weeks 1
ACUTE PHASE REACTANTS
Normal CRP and ESR
Abnormal CRP or ESR
Required score 6 or more, our patient 7.

36. MCTD DIAGNOSTIC CRITERIA
Kasukawa’s criteria
Our Patient
Raynaud’s or swollen fingers/hands +
Anti U1 RNP autoantibodies _
SLE Signs/ symptoms
Polyarthritis
Facial rash
Serositis -
Lymphadenopathy
Leucopenia
Thrombocytopenia

37. Scleroderma signs / symptoms Dermatomyositis signs/symptom
Sclerodactyly _
Pulmonary fibrosis
Vital capacity <80%
CO Diffusion <70%
Esophageal hypomotility
Dermatomyositis signs/symptom
Muscle weakness +
Increased CPK
EMG Abnormalities

38. DIAGNOSTIC SCORING OF THE PATIENT
SLE: 5/11 ACR Criteria.
Scleroderma : patient having score of 10 which is diagnostic of having definite scleroderma.
RA: Required is 6 or more, our patient has 7
MCTD: Fulfilling clinical criteria as the patient is having Raynaud’s phenomenon, SLE like features and dermatomyositis like features. Seronegative for anti U1 RNP antibodies. Hence the diagnosis of MCTD could not be established.

39. Final Diagnosis
Overlap syndrome

41. TREATMENT
NSAIDs
STEROIDS
NIFEDIPINE
PPI

42. FOLLOW UP OF THE PATIENT
Follow up of the patient was done 6 weeks after the initial therapy.
There was no progression of any of the autoimmune disorders to a full blown form.
Patient’s condition had improved significantly with the supportive management and initial treatment.

43. OVERLAP SYNDROME
The term has been used when two or more autoimmune diseases occur in the same individual simultaneously.
Example: The existence of Systemic lupus erythematosus, rheumatoid arthritis,scleroderma, dermatomyositis, polymyositis in various combinations.

45. SYSTEMIC LUPUS ERYTHEMATOSIS

46. DEFINITION
SLE is a systemic,autoimmune disease in which tissues and multiple organs are damaged by pathogenic auto antibodies and immune complex formation

47. CLINICAL FEATURES : Skin involvement like malar rash , discoid rash
Arthritis
Oral ulcers
Serositis (pleuritis or pericarditis)
Renal involvement
Neurologic disorder (seizures or psychosis)
Hematologic disorder (hemolytic anemia, leukopenia, thrombocytopenia)
Raynaud’s phenomenon

49. INVESTIGATIONS All baseline investigations.
Complete autoimmune profile
ESR
CRP

50. MANAGEMENT Education of the patients regarding nature of illness.
Supportive management like analgesics, NSAIDS, hydroxychloroquine.
Steroids may be required in combination with immunosuppressants like methotrexate , azathioprine or MMF.
Patients inadequately responding to standard therapy may given a trial of BELIMUMAB which targets B cell growth factors.

51. RHEUMATOID ARTHRITIS

52. DEFINITION
It is a long lasting autoimmune disorder that primarily affects joints typically resulting in swollen, warm and painful joints.
The hallmark of RA is inflammatory synovitis that presents in a symmetric distribution

53. CLINICAL FEATURES
Typical presentation is with pain, joint swellings and stiffness of small joints of hands, feet and wrists.
constitutional symptoms: fatigue, anorexia, weight loss, generalized weakness
There needs to be involvement of multiple joints, but some joints are never involved in RA:
• DIPs
• Joints of the lower back

54. EXTRA ARTICULAR MANIFESTATIONS
Cutaneous and vascular features
Ocular involvement
Cardiac and pulmonary involvement
Neurological complications
Vasculitis
Hematological involvement
Lymphatic involvement
Amyloidosis , a rare complication.

55. To monitor disease damage
INVESTIGATIONS
To establish diagnosis:
Clinical criteria
ESR and CRP
RA factor and anti CCP antibodies
USG /MRI
To monitor disease damage
X-rays
Functional assessment

56. MANAGEMENT General measures DMARD’s (Mainstay of management)
Corticosteroids
Biological therapy (high disease activity despite adequate treatment with DMARD’s)

57. SYSTEMIC SCLEROSIS

58. It is four times more common in females
Generalized disorder of connective tissue affecting skin, internal organs and vasculature.
T lymphocytes invading skin , abnormal fibroblast activation, increased extracellular matrix and thus resulting in symmetrical thickening, tightening and induration of skin and internal organs
It is four times more common in females
Progressive disease involving the skin and connective tissue which involves increased deposition of collagen in small arteries and connective tissue and sclerotic changes in skin and internal organs.

59. Patterns Limited cutaneous systemic sclerosis:
affects face and distal limbs predominately
Diffuse cutaneous systemic sclerosis:
affects trunk and proximal limbs predominately
Scleroderma (without internal organ involvement)
tightening and fibrosis of skin

60. CLINICAL FEATURES: Diagnosis: Skin Musculosketal features
Raynaud’s phenomenon
GIT, Pulmonary and Renal involvement.
Diagnosis:
Mostly Clinically
anti-scl-70 antibodies associated with DCSS
anti-centromere antibodies associated with LCSS
ANA positive in 90%

62. DERMATOMYOSITIS

63. DEFINITION
It is an autoimmune disorder characterized by an inflammatory process that affects the skeletal muscles and the skin.

64. CLINICAL FEATURES
Features of polymyositis i.e. symmetrical proximal muscle weakness.
Characteristic skin lesions i.e. heliotrope rash, gottron’s papules which are scaly erythematous or psoriasiform plaques occurring over extensor surfaces of PIP & DIP joints.
Periungual nailfold capillaries

65. INVESTIGATIONS Muscle enzymes (aldolase, CPK) EMG
Muscle biopsy (gold standard)
MRI (in case myositis is patchy and muscle biopsy is normal)
CT chest/ abdomen if malignancy suspected.

66. MANAGEMENT Oral corticosteroids 1 mg/kg daily
I/V steroids (if involvement of respiratory or pharyngeal muscles )
Immunosuppressive therapy

67. MIXED CONNECTIVE TISSUE DISEASE

68. DEFINITION
This is an overlap condition in which there are clinical features of SLE , systemic sclerosis , myositis and Rheumatoid arthritis with the presence of anti U- 1 RNP antibodies.
MCTD was first recognized by Sharp and colleagues in 1972

69. Clinical presentation
EARLY FINDINGDS:
Low grade fever
Swollen hands
Malaise , easy fatigability
Arthralgias/arthritis
Myalgias
Raynaud's phenomenon

70. Unusual findings
Neurological involvement like trigeminal neuralgias , aseptic meningitis
Serositis
Digital gangrene
Pulmonary hypertension
Polymyositis
Esophageal hypomotility
Hematologic abnormalities like leukopenia , thrombocytopenia
Cardiac involvement

71. DIAGNOSTIC CRITERIA Common symptoms
a. Raynaud’s phenomenon
b. Swollen fingers or hands
Features of SLE , systemic sclerosis , and polymyositis
Anti-RNP antibody

72. LABORATORY STUDIES CBC Urine R/E Routine blood chemistry
Muscle enzymes if myositis
Lipase /amylase if pancreatitis
Anti U1 RNP antibody
Antinuclear antibodies
High titer speckled fluorescent anti nuclear antibody is specific of MCTD (FANA)

73. Other immune studies Rheumatoid factor is frequently detected
Antiphospholipid antibodies
Other lupus specific antibodies are absent i.e. anti dsDNA
C3 and C4 complement levels are more likely be depleted in lupus than in MCTD

74. IMAGING Chest radiography - for infiltrates, effusion cardiomegaly
Echocardiography
Ultrasonography/CT scanning
MRI - Used to assess neuropsychiatric signs or symptoms

75. TREATMENT
Arthritis/arthralgia :nonsteroidal anti-inflammatory drugs (NSAIDs) and hydroxychloroquine.
Low-dose oral corticosteroids or low-dose methotrexate : refractory synovitis
PPI : Reflux esophagitis
Calcium channel antagonists : raynaud,s
Phosphodiesterase inhibitors, endothelin receptor antagonists, or prostaglandins : pulmonary hypertension.

76. FOLLOW UP
With stable disease approximately every 2-4 months and perform routine laboratory evaluation, including CBC count and chemistry studies.
Patients with active disease are typically seen approximately every 3-6 weeks, depending on the severity of disease.

77. Undiffrentiated connective tissue disease
The diagnosis of UDCTD is used to those patients with features strongly suggestive of autoimmune rheumatic diseases but who do not fulfill the criteria of any one of the disorders.
Ex: Raynaud’s phenomenon, polyarthritis, rash, myalgias. This entity may evolve into a specific disease or may persists unchanged over years or may even disappear

78. CONCLUSION
Various autoimmune disorders can coexist in a same individual even if they do not fit into diagnostic criteria of a broader term ie MCTD.They may progress into a full blown clinical form of any one of the disorder or may remain quiscent for a number of years. Patients who are seronegative for a particular disease cannot be excluded for not having a disease if they are fullfiling the clinical criteria.