Autoimune disorder of skin and muscle. Female prevalence high...skin rash in female

2. Case
Presentation
• Dr .SADAF MALIK (1st year PGR).
• Supervized by
• Dr. Sahibzada Mahmood Noor
• Dr. Muhammad Majid Paracha
• Dr. Abdul Quayyum khan
• Dr. Kashif kamal
• Department of Dermatology
• Lady Reading Hospital,Peshawar.

3. PATIENT
PROFILE
• NAME: ABC
• AGE: 5O years
• Gender: Female
• Occupation: Education
department
• ADDRESS: Peshawar.

4. CHIEF COMPLAINTS
• Redness and swelling of the face : 6 weeks.
• Progressive proximal muscle weakness : 01 month.
• Erythema of the trunk and swelling of extremities: 01month

7. Pertinent facts
• Diagnosed case of CA Breast
• Chemotherapy ( methotrexate, 5FU, cyclophosphamide)
• Operated upon twice since 2011.
• Family history: Insignificant.

8. Local examination
• Face….Erythema and swelling of face (cheeks ,periorbital area and
forehead)
• Upper limbs and neck…..erythema with telengiectasias on upper trunk.
• Scalp….diffuse alopecia.

9. Systemic examination
• Musculoskeletal :Muscle power was 3/5 in proximal muscles of both upper
and lower limb.
• Difficulty in sitting up from sitting position and combing her hair.

10. vitals.
BP……….160/100
PULSE….76 / min
TEMP…..98.6 F
R/R………18/min

11. Diagnosis
Based on history and
examination.
Dermatomyositis

12. How to investigate
this patient?
1.Muscle enzymes (Serum CK, Aldolase, LDH,
AST)
2.EMG
3.Muscle biopsy
4.MRI
5.Autoantibodies

13. Investigations
• COMPLETE BLOOD COUNT
HB….12.4g/dl
TLC… 3300
PLT…..64000
• SERUM CPK…6985 U/L
• SERUM ALDOLASE…32 U/L (2.5-10)
• ESR…110
• ANA….NEGATIVE

14. INVESTIGATIONS
…CONT
MUSCLE BIOPSY
• Biopsy taken from right upper arm
(biceps)
• Showing no pathological changes,
• No variation in muscle fibre size,
• No atrophy or dystrophy.
• No evidence of myositis or any
malignancy.

15. What are the
causes of
inconclusive
muscle
biopsy?
• If biopsy is not taken from weak
muscle.
Preferably triceps
• If myositis is patchy.

16. What are the
implications for a
treating physician
regarding muscle
biopsy?
• Muscle for biopsy should be
specified
• Surgeons biopsy deltoid muscle for
convenience
• Deltoid muscle involved late in
disease.

17. EMG
• Characteristic EMG findings suggestive of myositis.

18. Objective tests for Muscle
involvement
EMG and Muscle biopsy
EMG or Muscle biopsy
MRI or Muscle ultrasound
OR
PLUS
oBrown VE, Pilkington CA, Feldman BM, Davidson JE. An international consensus survey of
the diagnostic criteria for juvenile dermatomyositis (JDM). Rheumatology 2006;45:990–3

19. INVESTIGATIONS…cont
PT ,APTT/ INR….NORMAL
RFTs….NORMAL
LFTs……NORMAL
S/E……..NORMAL
URINE R/E….NORMAL
FBS….206 mg/dl

20. DIAGNOSTIC CRITERIA OF DM
BOHAN AND PETER CRITERIA
Typical rash of dermatomyositis
PLUS
1.Proximal symmetrical muscle weakness determined by physical examination
2.Muscle biopsy showing myositis (degeneration , regeneration, necrosis ,phyagocytosis)
3.Elevation in serum skeletal enzymes (CK, Aldolase, serum glutamate
oxaloacetate,pyruvate transaminase,LD.)
4.Characteristic EMG pattern of myositis (triade of short, small ,polyphasic motor unit
potentionals,fibrillation,positive sharp waves)
• 5. Typical skin rash of DM (heliotrope rash and gottron’s papules)
• DEFINITE DM…Typical rash of DM + any 3 0F 1-4.
• PROBABLE DM..Typical rash of DM + any 2 OF 1-4.
• POSSIBLE DM… Typical rash of DM +any 1 OF 1-4

21. EXCLUSION
CRITERIA
• 1. Central or Peripheral neurologic
desiese
• 2. Muscular dystrophies
• 3. Granulomatous and Infectious
myositis
• 4. Metabolic and Endocrine
myopathies.
• 5. Myasthenia gravis.

22. So our
diagnosis
based on this
criteria ;
• Typical rash of Dermatomyositis.
• Proximal symmetrical muscle
weakness
• Elevation in serum muscle
enzymes.
• Characteristic EMG findings

23. DERMATOMYOSITIS
associated with Ca
Breast.

24. WHAT
SHOULD BE
THE
TREATMENT
PLAN ?
• Corticosteroids
• Immunosuppressants
• Immunoglobulins
• Biologic agents
• Plasma pharesis

25. DURING
HOSPITAL
STAY…
• She had pulse of methylpred
• She was started on I.V
Dexamethasone 3 CC
• Her erythema and swelling
improved.
• CK levels gradually decreased.
BUT
• she developed Nasal
Regurgitation of fluid and
Difficulty in Talking on 5th day of
admission.
• She also developed Leucopenia

26. So what is TRUE predictor of disease activity ?
• CK levels usually parallels disease activity .
• May be NORMAL in patients with active disease.
• CK levels fall with improvement in muscle strength
• Muscle strength may deteriorate with falling CK levels.
• So our main objective should be improvement in muscle strength rather
then chasing or treating CPK levels.
o Therapeutic targets in patients with inflammatory myopathies: present
approaches and a look to the future. Dalakas MC. Neuromuscul Disord.
2006 Apr; 16(4):223-36.

27. So what to do next?
• Can we give immunosuppressants ?
• If not, then what else?
• I.V IMMUNOGLOBULINS

28. TREATMENT IN HOSPITAL
• We started her on I.V. immunoglobulins in dose of 0.4 g/kg/day for 5
days.
• Her nasal regurgitation of fluids and dysphagia settled.
• She was given granulocyte colony stimulating factor for decrease in TLC.
• Regular physiotherapy of weak muscles.

29. Progress in Hospital…
• Her proximal muscle weakness in upper limbs improved and her muscle
power is 4/5 in both upper and lower limbs.
• CK level decreased progressively from 6985 u/l at admission to 206 u/l .
• Erythema and swelling of face and body improved.
• On her 5th visit for chemotherapy, her previous medications were stopped
and replaced by capecitabine,which has low incidence of
myelosuppression.

30. What should be future plan?
• Gradual tapering of steroids.
• 2ND session of immunoglobulins.
• Regular disease monitoring including side effects of drugs being given.
• REGULAR FOLLOWUP WITH ONCOLOGIST FOR CARCINOMA BREAST.

31. MANAGEMENT
GENERAL
SPECIFIC

32. MANAGEMENT
GENERAL MEASURES
Bed rest in severe
myositis.
Photo protection with sun
screens in skin disease.
Physiotherapy of weak
muscles.

33. Treatment options
1.SYSTEMIC CORTICOSTROIDS
2.IMMUNOSUPPRESSIVE THERAPY
3.I.V. IMMUNOGLOBULINS
4.BIOLOGIC THERAPY.
5.PLASMAPHERESIS

34. Step 1-Corticosteroids
• Oral prednisolone is initial treatment of choice and should not be delayed
in order to perform muscle biopsy.
• 0.5 to 1 mg /kg /day as early as possible for at least 4 weeks.
• The dose can be reduce by 20 to 25% every 4 weeks until the daily dose of
5 to 10 mg is reached and a stable dose of steroid is maintained for an
other year .

35. CONTI… • NOTE
• With GC use CK and muscle
strength should be monitored .
• Patient with long period between
muscle symptoms onset and
starting of drug treatment or less
likely to present a complete
response to GC.
• Those who do not show clinical
improvement with GC
,reassessment of diagnosis i-e
steroids induced/malignancy.
• Those present with reactivation of
disease by tapering GC dose ,than
immunosuppressant's are used.

36. Corticosteroids…cont.
• Efficacy of prednisolone is
determined by objective increase
in muscle strength and activities of
daily living which almost always
occurs by third month of therapy.
• If patient does not respond in 3
months, tapering of steroids
should be accelerated.

37. Corticosteroids…cont.
I.V. pulse methylprednisolone
(500mg-1g/day) can be given for 3
days followed by oral steroids.
Can be used as 1st line medication
in patients with;
• Severe disease
• Systemic manifestations.

38. Step 2-
Immunosuppressants
• When to start immunosuppressant
is not clearly defined.
• Some clinicians start it along with
steroid therapy.
• Other may add it later on if Steroid
tapering becomes difficult due to
relapse of disease or steroid
resistance.

39. Immunosuppressants..cont.
• Azathioprine : 2 –3 mg/kg/day
P.O.
• Methotrexate : 20-25 mg weekly.
P.O.
• Cyclosporine: 3 to 5 mg/kg/day
• Mycophenolate Mofetil: 1 to 1.5
gm twice a day P.O
• Cyclophosphamide: 0.5 to 1
gm/m2 I.V. every 3-4 wks. It is of
benefit in ILD.
• OTHER DRUGS;
• Oral tacrolimus 0.075 mg/kg /day,
leflunomide.

40. Step 3-IV
Immunoglobulins
• One may use it as step 2 for very
active disease
OR
• Use it as step 3 in in situations of
exacerbations of disease activity,
despite continuing steroids plus an
immunosuppressant.
• OR
• Refractory cases
• Contraindication of
immunosuppresents .

41. MOA of
immunoglobulins
IVIG is an immunomodulating
agent.It causes ;
• Modulation of complement
activation
• Saturation of Fc receptors on
macrophages
• Suppression of various
inflammatory mediators, including
cytokines, chemokines, and
metalloproteinases.

42. Initial
duration of
treatment
• Initial treatment should be
carried out over a period of 6
months in order to determine the
efficacy of treatment with IVIg.

43. IV Ig dosing
• 2 g per kg body weight
per treatment cycle over a
period of 2-5 consecutive
days.
• No clear evidence of
efficacy with lower doses,
strict adherence to the
aforementioned dose
recommendations is
required.

44. Interval b/w
infusions
• Initially IVIg therapy should be
administered every 4 weeks.
• If a good clinical response is
achieved,the interval can be
increased gradually to a
maximum of 6 weeks.
Can we extend the interval
beyond 6 weeks?
• However longer intervals
between infusions are not
recommended because of the
half-life of IVIG is approximately
3 weeks).

45. Evaluation of
therapeutic efficacy of
I.V. immunoglobulins
• Muscle strength is the most important
parameter for evaluating the efficacy
of treatment in DM.
• Auto-antibody titers, and muscle
enzymes are not reliable indicators of
clinical improvement.
• A response can be detected from the
2nd treatment cycle
• 3-4 treatment cycles are often
required before a significant
improvement in symptoms is seen.

46. Adverse
effects of I.V
IG.
• In less than 5% of patients.
• The most common adverse
effects occur soon after
infusions
• include ; Anaphylactic
reaction, headache,
flushing, chills, myalgia,
wheezing, tachycardia,
lower back pain, nausea,
and hypotension.

47. Adverse
effects..
Cont.
Other rare side effects
include
• Eczematous reaction
• Acute renal failure
• Thrombosis ,DIC, Transient
neutropenia.
• Transmission of Hepatitis
C.

48. Monitoring
• CBC with DLC.
• LFTs…monitored every 3
months to exclude sub-
clinically transmitted
hepatitis.
• RFTs
• Hepatitis screening

49. PLASMAPHERESIS
• Plasmapheresis is used in the treatment of refractory cases to remove
circulating autoantibodies and immune complexes.
• Given the lack of efficacy, the cost and the potential for complications,
there is little justification for using plasma exchange in patients with
myositis.

50. Long term monitoring
• CPK and Muscles strength assessment
• Auto antibodies titers.
• Disease monitoring on monthly basis
• Muscle enzymes along with clinical assessment of muscle strength.
• Annual physical exam. is useful to monitor potential toxicity due to
therapy.
• Malignancy evaluation for at least first 3 years after diagnosis.

51. PROGNOSIS
• Varies and depends on clinical condition.
• Patient without muscle disease seem to
have good prognosis.
• About 50% usually respond to therapy.

52. Adverse prognostic factors
Delay in treatment
Severe dysphagia
Respiratory difficulty
Associated malignancy
Relapses can occur at any time

53. Follow up
Disease free on low
dose of steroids
Regular follow up with
oncologist.
Presented with relapse
and metastasis
No response to IVIG so
far.

54. References
• Eur J Dermatol 2009 ; 19 (1) : 90-98
• J Indian Rheumatol Assoc 2004 : 12 : 58
– 69
• Rooks Text Book of Dermatology

55. THANK YOU