40 yr old mrs stella rani has come to the hospital with c/o difficulty in using all 4 limbs-last 7 monthsBlackish discoloration face and hands-6 monthsDifficulty in swallowing 2 months Pain over the both great toes 1month

She was apparently normal 7 months ago when developed pain over the both thighs followed by fever, she took treatment, fever subsided in 3 days but she noticed weakness of both legs, mainly in the proximal region, which is insidious in onset and slowly progressive in natureh/o difficulty in getting up from squatting and lying posture, climbing the stairs -7monthsDifficulty in lifting the hand above the head, combing the hair and bringing the food to mouth-6 monthsh/o difficulty in lifting the head from the pillow-4 monthsDifficulty in mixing the food- 2 monthsDifficulty in holding the chapels last 2months

h/o hyper pigmentation over the face, chest and neck-6 months, non itchy h/o dysphagia .-last 2 months , started with solid food now even for liquid, progressive,

mainly during initiation of swallowing and associated with throat painh/o pain over the both great toes and 2nd toes for last 1month h/o excessive hair loss +

No h/o difficulty in turning in bed from side to sideNo h/o diurnal variation of weaknessNo h/o twitching of musclesNo h/o sensory symptoms, cerebellar and posterior column symptomsNo h/o seizure

No h/o ptosis, diplopiah/o dryness of mouth +No h/o dryness of eyesh/o cough with expectoration, white colour, scanty sputumh/o dypnea on exertion +No h/o feverNo h/o PhotosensitivityNo h/o Altered bowel and bladder habitsh/o Head ache+No loss of appetite but loss of weight+

PAST HISTORY She had PT 10 years back, completed ATT No H/O similar complaints in the past No H/O DM,SHT,BA,CAD FAMILY HISTORY married, has 4 children, no h/o spontaneous abortion no other family member suffering from similar illnessMenstrual history RMP 3/30 DAYS TREATMENT HISTORY not on any chronic treatment no h/o drug allergy

Pt moderately built and nourished

Conscious ,oriented ,afebrile pallor+ No icterus/no cyanosis/no clubbing/no PE/no GLA no thyromegaly vitals -BP-150/90 mmHg, PR-86/min, RR-18/m regular, thoraco abdominal

Skin dark red rusty erythematous lesions over the malar region, fore head, both shoulder, upper chest and back (V sign, shawl sign present)Erythematous lesion over the MCP and PIP-Gottron papules and sign +Cold great toes with tenderness +

ORAL CAVITY- poor oral hygiene, ulcer over the left upper buccal mucosa , carie`s tooth

Higher function- normalCranial nerves- palatal movements equal on both side but sluggish, otherwise normal CN examinationSpino motor system

RT LT bulk- generalized wasting+

Arm 28cm 28cm Fore arm 24cm 24cm Thigh 42cm 42cm Leg 24cm 24cm

Tone - normal on both sidePower - shoulder 2/5 both side Elbow 3/5 both side wrist 4/5 both side hand grip good hip 2/5 ,knee 3/5, ankle 4/5DTR preservedPlantar b/l flexor , other superficial reflexes normalSensory system normalNo cerebellor sign No involuntory movements No fasiculation Gait- waddling gait

CVS- S1S2+, No murmurRS- NVBS+, No added sounds

ABDOMEN- soft , Epigastric tenderness+ No organomegaly no FF

Inflammatory myopathyDermatomyositis

orDermatomyositis with overlap syndromeAnemiaSHTOld PT

T.Prednisalone 40 mg odT.Ranitidine 150mg bdInj.Ampicillin 1g iv tidInj.Deriphylline 2cc iv bdT.Amlodipine 5mg odSupportive measures

HB 9.4RBS 122TC 9200UREA 18DC P60L35E5CREATININE 0.9ESR 17/32Na 136MCV 86.7K 3.9MCH 25.5Cl 98MCHC 29.7HCO3 23PCV 24PLATELETS 1.78LAcsURINE ROUTINE-ALB/sug-nilDEP-1-2 pc RBC 4.16 million

Rheumatologist advised to transfer the patient to GGH for evaluation & management

CPK-35 RA factor-negativeALT-316 CRP- negative AST-114 ANA-POSITIVE LDH-2461 anti dsDNA-NEGATIVECHL-262 TGL-287

ECG-WNLECHO-NORMAL STUDYUSG abdomen- normal studyX ray both hands-soft tissue swelling, no calcification, no osteoporotic lesionX ray elbow-soft tissue swellingHRCT chest-cystic ectasia of bronchi in the posterior segment of Rt upper lobe,

Ground glass opacity noted in the basal segments of both Lower Lobe L>R

DERMATOLOGY- confirm the DMNeurology- inflammatory myopathy

EMG fixed on 13/4/10Cardiac evaluation- normalChest physician opinion- DM with ILD, old PT seqeule MGE- UGI scopy normal, colonoscopy fixed on 19/3/10, barium swallow to be doneDental opinion-chronic gingivitis, traumatic ulcer over the left buccal mucosaENT opinion- no growth in the pharynx, vocal cords normal

Inflammatory myopathyDermatomyositisILDANEMIASHTOLD PT SEQEULE

SteroidsMethotrexate/cyclophosphamideHydroxy chloroquine

She is improving..

Idiopathic InflammatoryMyopathies (IIM)Heterogeneous group of autoimmune syndromes characterized by chronic muscle weakness and muscle inflammation, systemic complications

Adult polymyositis (PM)Adult dermatomyositis (DM)Juvenile myositis (DM >> PM)Malignancy-associated myositisMyositis in overlap with another rheumatic diseaseInclusion body myositis (IBM)Other uncommon forms

Prevalence 1/100,000

Estimated annual incidence of 1.9-7.7 per million persons

Women more commonly affected 2:1

Peak age of onset 40-50

The cause is unknown, but it may result from either a viral infection or an autoimmune reactionSome cases of DM are a paraneoplastic phenomenon, indicating the presence of cancer and is usually pre-existent, with removal of the cancer resulting in remission of the DM. Genetic HLA DR3,DR5,DR, a-TNF polymorphismImmune abnormal T cell activityInfectious viral agents, Toxoplasma, BorreliaDrugs Hydroxyurea, penicillamine, statin, quinidine, phenylbutazone

Dermatomyositis is probably caused by B cell and complement-mediated (terminal attack complex) vascular inflammation, while polymyositis is caused by the direct cytotoxic effect of CD8+ lymphocytes on muscle. However, other studies of cytokines suggest that some of the inflammatory processes may be similar. A recent report has linked tumor necrosis factor (TNF) abnormalities with dermatomyositis.

Progressive, gradual (over many months), symmetric muscle weakness difficulty with everyday tasks that require proximal musclesFine motor skills may be affected later in the disease course (but are common early in IBM)Normal sensationPharyngeal and neck flexor muscles are often involved may have dysphagia or head dropMay have respiratory involvement late in the presentationOcular and facial muscles are sparedTendon reflexes preservedMyalgia and muscle tenderness may occur, early

in the disease

Heliotrope rash: purple discoloration on the upper eyelids with peri orbital edema Gottrons papules: raised scaly violaceous rash over PIP and MCP joints Erythematous rash: occurs on knees, elbows, neck and anterior chest (V sign), back and shoulders (shawl sign)Raynauds phenomenon, subQ calcifications, periungal erythemaMechanic`s hand- irregular, thickened, distorted lateral and palmar surface of fingers

CD8 + T cells invade muscle fascicles(endo mysial invation), surround healthy muscle fibers and result in phagocytosis and necrosis

B cell and CD4+ T cell infiltrates within the perivascular or interfascicular space, antibodies activate C3 and MAC complex activation of cytokines and chemokines

Spinal muscular atrophy, ALS (use EMG to help)Muscular dystrophies develop over longer periodGuillain-Barre, polio, West Nile virus, neurotoxin acute muscle weaknessAZT - causes a mitochondrial myopathyDrug reaction- Amphotericin B, Heroin, Amiodarone, Colchicine, chronic laxative use, Glucocorticoids, Statins, Cyclosporine, Gemfibrozil, Alcohol, CocaineSteroid induced muscle weaknessPolymyalgia rheumatica, fibromyalgia muscle tenderness, pain with movementConnective tissue diseasesEndocrine Hypo and hyperthyroidism

Muscle enzymes CK, AST, ALT, LDH, aldolase

CK sometimes normal in active DM and IBM but always elevated in active PMESR and CRP are often normal and are not reliable indicator of disease activityAntibodiespositive ANA in > 75%Anti Jo-1: found in 25%, 80% with this positive have lung involvement (antihistidyl transfer RNA [t-RNA] synthetase)Anti Mi-2: found in 5-10%, more common in dermatomyositis Anti SRP associated with rapidly progressive PMEMG short duration, low amplitude polyphasic units on voluntary activation increased spontaneous activity with fibrillations, complex repetitive discharges, positive sharp wavesMuscle biopsyMRI can detect early and patchy involvement, can guide biopy

Symmetric proximal muscle weaknessElevation of serum muscle enzymes: CK, aldolase, AST, ALT, LDHAbnormal electromyogram (EMG) Characteristic muscle pathology degeneration (breakdown) and regeneration (healing)inflammatory cells attacking muscle

Muscle painPositive Anti-Jo-1 Arthritis/arthralgiaSystemic inflammatory signs: fever, CRP, ESR4+ of them = PM

Skin rash of DM: Gottrons papules or sign, heliotrope rash4+ and skin rash = DM

Extramuscular manifestations Systemic: fever, weight loss, arthralgias and raynauds phenomenonJoint contractures common in juvanile DMGI: dysphagia (upper 1/3 striated muscle)Cardiac: AV conduction defects, tachyarrhythmias, dilated cardiomyopathy, CHFPulmonary: respiratory muscle weakness, interstitial lung disease calcinosis -Subcutanious calcifications common in JDM

Assoctation with Malignancy

Most common include ovarian, breast carcinoma, melanoma, colon, non-Hodgkins lymphoma Nasopharyngeal cancer common in AsiansSearch for an occult malignancy in all adult cases of DM should be done.

Can associated with systemic sclerosis or mixed connective tissue disease

Very rarely with RA , SLE or sjogren`s

DM with SS will have a specific anti nuclear antibody, anti-pm/scl, directed against a nucleolar protein complex

Antisynthetase syndrome

A subset of pts with PM and DM can have a group of findings including inflammatory arthritis, Raynaud`s phenomenon, ILD associated with certain auto antibodies( anti jo-1 )

Amyopthic DM or Dermatomyositis sine myositis

Skin lesion without muscle involvement

another subset of patients with dermatomyositis have controlled myopathy but continue to have severe and sometimes debilitating skin disease; this condition has been termed postmyopathic dermatomyositis.

Juvenile dermatomyositis is a systemic vasculopathy, affecting mainly the skin and muscle.It differs from the adult form of dermatomyositis by the presence of vasculitis of the small blood vessels, which can involve the gastrointestinal tract and myocardium, besides skin and muscle. Calcinosis is an additional feature that is present in juvenile dermatomyositisJuvenile dermatomyositis is not associated with development of malignancies, unlike adult dermatomyositis.

Other features

Vasculitis and skin ulcerationMyocarditis with arrhythmias can occurArthralgia/arthritis with contracturesMuscular contractures decreased joint mobilityGastrointestinal dysfunctionPulmonary involvementCalcinosis (after 12 years)

*

White, male, and over the age of 50Onset more insidious than PM or DM over yearsAsymmetric distal motor weakness is commonCK- mostly normalMuscle biopsy-intracellular vacuoles with tubular or filamentous inclusions in the nucleus or cytoplasm

Glucocorticoids: start with high dose prednisone 1 mg/kg/day, taper after 4 weeks until lowest dose possible reachedCaution as long term use may cause muscle weakness, osteoporosis75% will require additional medications

Immunosuppressants: Azathioprine-3mg/kg daily, Methotrexate-7.5mg/wk, Cyclophosphamide-0.5-1g/monthly, Chlorambucil, Cyclosporine, Mycophenolate mofetil-2.5mg/day

Immuno modulators IV Ig improved not only strength but also the underlying immuno pathology, benefit short lived, Repeated infusion q6-8 weeks

Dose 2g/kg divided over2-5 days per course

Plasmapheresis no statistical difference between those given immunosuppressants and those who received plasmapheresis

For skin rashes - Limit sun exposure, hydroxychloroquine

For both DM and PM, 5 year survival is 95%, 10 year survival is 84%

Death is usually due to pulmonary, cardiac or systemic complications

Poor prognostic factors older age at diagnosis, ethnicity, bulbar involvement, delayed treatment, cardiac and pulmonary involvement

No correlation with prognosis - CPK level, grade of disability and degree of muscle weakness at presentation

Choy and Isenberg. Treatment of dermatomyositis and polymyositis. Rheumatology. 2002; 41: 7-13.Dourmishev and Wollina. Dermatomyositis: immunopathologic study of skin lesions. Acta Dermatoven APA. Vol 15, No 1. 2006.Harrisons Internal Medicine, 17th edition.Miller, M. Clinical manifestations and diagnosis of adult dermatomyositis and polymyositis UpToDate Online. Last updated February 15, 2008.Miller, M. and Rudnicki, S. Initial treatment of dermatomyositis and polymyositis in adults. UpToDate Online. Last updated June 5, 2008.www.neuropathologyweb.org. Northeastern Ohio Universities College of Medicine.

*