A Case of a 53 year-old Woman with SLE-Dermatomyositis Overlap

Honey Mabelle C. Abergas, MD;  Joselito C. Javier, MD;  Agnes D. Mejia, MD

PRESENTATION OF THE CASE

This is a case of a 53 year-old female presenting with body weakness, rash and a breast mass admitted at the medicine ward of the Philippine General Hospital (PGH). This paper will discuss the clinical presentation, diagnosis and prognosis of an overlap syndrome of dermatomyositis (DM) and systemic lupus erythematosus (SLE) and its association with malignancy.

Our patient was apparently well with no known co-morbidities until 10 months prior to admission (PTA) when she had red itchy  papular rashes on the anterior chest wall aggravated by sun exposure. She also had a tight and thickened sensation of the skin and a firm, non-tender mass on her left breast.

2 months PTA, the papules changed in color from red to violaceous, then to dusky red that spread to the whole torso, back, face, both upper extremities and knees. She also experienced easy fatigability, elbow and shoulder joint pains, difficulty standing up from sitting position but not with walking, dysphagia, minimal hair loss and hoarseness of voice.

1 month PTA, still with the above symptoms, she developed left-sided weakness and slurred speech. She was admitted in a local hospital and a left acute cerebellar infarct was confirmed by cranial CT scan. She was discharged after 2 weeks with improvement in her speech but was dependent in all her daily activities.

1 week prior to admission, the severity of her weakness increased. This time it was bilateral with difficulty raising her head when lying on her back. Persistence of the symptoms prompted her to consult at PGH.

Review of medical history revealed no other illnesses except for those mentioned above. She had no vices and denied any illicit drug use. She lived with her husband and with her four healthy children. Her first pregnancy ended up with spontaneous abortion at 8 weeks age of gestation.  Her OB score is G5P4 (4014). Her mother had kidney disease while her father had pulmonary tuberculosis.

Upon admission, the patient was stretcher-borne yet coherent, afebrile and with stable vital signs. Pertinent findings on physical exam (Figure A) included violaceous to dusky red papules and plaques from head to knee, with scaling more prominent in the scalp, forehead, malar area (with nasolabial fold sparing), lips, and chest (sparing the breasts); heliotrope patch at periorbital area with periorbital edema; discoid rash on pinnae of ears; oral ulcers; erythematous patch over knuckles of the right hand (Gottron’s sign);  periungual telangiectasia and cuticular dystrophy, both hands, and hyperpigmented scaly plaques on both knees and lateral sides of both thighs.

An 8 x 10 cm, firm, nontender mass in the upper outer quadrant of her left breast was noted with some palpable lymph nodes in the left axilla. However, no discharge, nipple retraction nor ulceration was noted. Neurologic exam showed muscle strength of 4/5 on all extremities, and dysdiadochokinesia on the right. There were equal palatal elevation, midline tongue, full extraocular muscle, +2DTRs, no clonus and no Babinski reflex.

Our clinical impression was SLE-DM overlap; left breast mass, likely malignant; CVD, left cerebellar infarct, to consider antiphospholipid syndrome and systemic sclerosis.

Complete blood count showed mild anemia and persistent lymphopenia (Table 1). Urinalysis and urine culture showed sterile pyuria. Blood chemistry: hypoalbuminemia, normal creatine kinase-total and ck-mb,  elevated AST (Table 2). Initial work-ups for antiphospholipid syndrome were all normal (Table 3). Antinuclear antibody was +4 with no pattern available. Erythrocyte sedimentation rate was elevated.

She was given hydrocortisone 100mg IV q8h, hydroxychloroquine 200mg po od, calcium carbonate 500mg po bid, esomeprazole 40mg po bid, simvastatin 20 mg po od, aspirin 80 mg po od, clobetasol  cream plus petroleum jelly bid on affected areas, and mupirocin ointment bid on infected skin lesions. Improvement of proximal muscle strength was seen on the 4th hospital day. Hydrocortisone was shifted to oral prednisone 50mg /day. Bedside rehabilitation was started on the 7th hospital day. Core needle biopsy of the left breast mass revealed an invasive ductal carcinoma (Figure B). Skin punch biopsy revealed vacuolar interface dermatitis, positive for alcian blue stain (Figure C).

On the day of discharge (30th hospital day), she was able to sit alone and stand with support. Distal muscle strength was still 4/5 but proximal muscles were stronger this time. Skin rashes were still hyperpigmented yet erythema and scaling were markedly decreased. Periungual telangiestasia and cuticular dystrophy were resolved. She was able to tolerate liquids per orem. Her discharge diagnosis was SLE-DM overlap; Invasive ductal carcinoma, left breast; CVD, left cerebellar infarct.

Her home medications were prednisone 50 mg per day, hydroxychloroquine 200mg tab od, aspirin 80mg tab od, petroleum jelly on affected areas bid and calcium carbonate 500mg tab tid. Eventual plan was to do modified radical mastectomy of the left breast. Unfortunately, she was lost to follow-up.

TABLE 1: RESULTS OF HEMATOLOGIC EXAMINATION

 

DAY OF ADMISSION

DAY 7

DAY 11

DAY 23

Hemoglobin (120-140 g/dl)

113

84

96

104

Hematocrit (0.32-0.45)

0.34

0.28

0.29

0.33

MCV   ( 80 – 100 fL )

-

103

97

96

MCH   ( 27 – 31 pg)

-

31

31

30

MCHC   ( 320 – 360 g/L )

-

299

322

312

WBC count (4.0-10 x 109 /ml)

6.57

8.52

5.47

5.46

   Neutrophil (0.40-0.70)

0.69

0.91

0.75

0.76

   Lymphocyte (0.20-0.50)

0.21

0.16

0.16

0.16

ALC  (1500-3000 x 106 /ml)

1379

1363

857

873

   Monocyte (0.04-0.08)

0.1

0.04

0.07

0.06

   Eosinophil (0-0.6)

 

 

0.005

0.01

Platelet count   (150 – 450 x 103/ml)

240

201

263

229

ESR    (0-20 mm/hr)

 

 

 

52

Coombs’ test, both direct and indirect

negative

 

 

Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC), Absolute Lymphocyte Count (ALC), Erythrocyte Sedimentation Rate (ESR)

TABLE 2 : BLOOD CHEMISTRY RESULTS

 

DAY OF ADMISSION

DAY 4

DAY 13

DAY 17

DAY 23

Glucose  (mmol/L)

3.56

 

 

 

 

BUN  (mmol/L)

3.87

 

 

 

 

Creatinine  (umol/L)

37

 

 

 

 

Na  (mmol/L)

135

 

138

 

 

K  (mmol/L)

4.4

 

2.9↓

3.5

 

Cl  (mmol/L)

99

 

98

 

 

Ca (mmol/L)

 

1.88 (corr 2.38)

1.8 (corr 2.28)

 

 

Mg (mmol/L)

 

 

0.76

 

 

Albumin (mmol/L)

 

15↓

16↓

 

 

AST (u/L)

 

82↑

 

 

 

ALT (u/L)

 

35

 

 

 

ALP (u/L)

 

 

 

 

102

LDH (u/L)

 

 

 

 

385

CK Total (u/L)

 

114

 

 

42

CK mb (u/L)

 

7.37 sl↑

 

 

5.29

Blood urea nitrogen (BUN), Aspartate transaminase (AST), Alanine transaminase (ALT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH), creatine kinase (CK)

TABLE 3: ANTIPHOSPHOLIPID  ANTIBODY WORK-UP

KCT                (50-90 sec)

72    

DRVVT          (31-44 sec)

41

ACA  IgG       (up to 15 GPL U/ml)

13

ACA IgM       (up to 12.5 MPL U/ml)

9.84

Koalin Clotting Time (KCT), Diluted Russel Viper Venom Test (DRVVT), Anti-Cardiolipin antibody (ACA), Immunoglobulin G (IgG), Immunoglobulin M (IgM)

DISCUSSION

We are presented with a 53 year old female with body weakness, rash, photosensitivity and an invasive ductal breast carcinoma. Despite the fact that our patient had left cerebellar infarct with residual left-sided weakness, her weakness at the time of admission was noted to be symmetrical and proximal. With the proximal body weakness, Gottron’s sign and heliotrophe rash and a concomitant breast cancer, our diagnosis was  DM. On the other hand, her discoid and malar rashes with the nasolabial fold sparing, and oral ulcers suggest SLE. Periungual telangiectasia, cuticular atrophy, photosensitivity, positive ANA and lymphopenia are all nonspecific connective tissue disease findings. For this 53 year-old female; is this a case of DM alone or a DM-SLE overlap?

DM- SLE OVERLAP VS DM ALONE WITH CONSTITUTIONAL SIGNS AND SYMPTOM

An overlap syndrome is a combination of the major features of more than one rheumatologic disease in the same patient and often defined by a specific serologic test (1). To label a syndrome as “overlap”, it is necessary to identify a constellation of distinctive features that constitute a true syndrome. Overlap syndromes define patients exhibiting enough features to meet the diagnosis of several CTDs at the same time (2).

Our patient satisfied both the 1997 American College of Rheumatology criteria for SLE (Appendix A), and the Bohan and Peter criteria for DM (Appendix B). She had 6 out of 11 criteria for SLE: malar rash with nasolabial sparing, discoid rash, oral ulcer, photosensitivity, lymphopenia, and positive ANA (3,4). She also had symmetrical proximal muscle weakness, Gottron’s papule and heliotrphe rash, and elevated AST which according to the Bohan-Peter diagnostic criteria suggest probable DM (5, 14). Hence, a DM-SLE overlap.

On the other hand, using the DM/PM classification criteria suggested by Tanimoto (which has a sensitivity of 94.1% and a specificity of 95.2%), our patient met only 3 out of 8 criteria PLUS all 3 skin lesions for DM, namely: proximal muscle weakness, arthralgias and systemic inflammatory signs, and skin lesions such as heliotrope rash, Gottron's sign, erythema on the extensor surface of extremity joints (7) (Appendix C). Tanimoto requires at least 4 out of 8 criteria, plus 1 skin lesion. Nevertheless, since both the above standard criteria are satisfied, our impression still was DM-SLE overlap.

In 2005, Trayonav and his group suggested a novel classification of inflammatory myopathies (including overlap myositis and cancer-association) using overlap features and antibodies and clinical paraneoplastic features (with 87% sensitivity for overlap syndromes) (17). They proposed to abandon the Bohan-Peter classification because it overlooks the diagnosis of an overlap syndrome. The study showed that 60% of diagnosed idiopathic inflammatory myopathy [Polymyositis (PM) and DM] were found to have an overlap syndrome. Using this classification (14), our patient will fall under overlap myositis (DM) with SLE features (Appendix D).

There are several diagnostic tests useful in the assessment of patients presenting with DM-SLE overlap.

MUSCLE ENZYMES

Measurement of the serum CK level is traditionally the first step in the assessment of patients with idiopathic inflammatory myopathy (e.g. dermatomyositis). Generally, 80% to 90% of adult myositis patients show an increase in CK during the initial evaluation.  Our patient had normal CK total and Mb levels. Although muscle enzymes such as creatine kinase are frequently elevated in DM, they can be normal even in active disease with myositis (6). Normal CK is relatively more common in DM than in PM (14). Hence,measurement of other serum muscle enzymes, including aldolase, aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH), significantly improves the chance of diagnosing active myositis (14). The main disadvantage of these enzymes is that they are also elevated in liver diseases; therefore, the muscle source needs to be identified before interpreting the data. In our case, AST is elevated. However, ALT is normal; hence more likely that the muscle is the source of the elevated AST, and not the liver.

SKIN BIOPSY

Histopathologic findings of skin in DM are hyperkeratosis, vacuolization of the basal keratinocytes, melanin incontinence, perivascular lymphocytic infiltrate, and epidermal atrophy (8). In our patient, skin biopsy revealed vacuolar interface dermatitis (vacuolization of the basal keratinocytes). Staining with alcian blue revealed presence of mucin which can be found both in DM and lupus. However, no histopathologic skin features are specific for DM; most of the features are also seen in patients with SLE. (8) Thus, skin biopsy, even with alcian blue stain,  is rarely helpful in differentiating DM from SLE.

MUSCLE BIOPSY

Muscle biopsy remains the “gold standard” for the diagnosis of inflammatory myopathies such as DM (14). The features specific to DM include loss of capillaries, alterations in the morphology of capillaries, capillary necrosis with the deposition of complement products on the vessel walls, and, rarely, muscle infarcts, and perifascicular atrophy (Figure D – not our patient ), which is the hallmark for DM. Nevertheless, all the three sets of criteria for DM (Bohan-Peter, Tanimoto, Troyanov) never required the presence of a muscle biopsy as a prerequisite for diagnosis. It was even given the same weight as the other clinical criteria. While we were not able to do a muscle biopsy, the other clinical findings would suffice to confirm the diagnosis.

ELECTROMYOGRAM

Electromyogram (EMG) changes are usually nonspecific but can serve as useful indicator of myopathic changes, a reasonable measure of disease activity and practical guide for biopsy sampling. Abnormal electrical irritability in DM (and polymyositis) involves increased insertional activity, trains of positive sharp waves, and fibrillation potentials (14). As with muscle biopsy, the absence of EMG would prompt the use of the other clinical finding to clinch the diagnosis.

AUTOANTIBODIES

Identification of specific autoantibody strengthens the diagnosis. Positive low-titer ANA occurs in most cases, even in the absence of connective tissue disease. Anti-Ku antibodies are associated with myositis overlap with scleroderma or systemic lupus erythematosus (8). Autoantibodies associated with overlap syndrome may serve as markers of   responsiveness or resistance to corticosteroid treatment (17).

These autoantibodies are:

  1. antisynthetases (Jo-1, PL-7, PL-12, OJ, EJ, KS)
  2. scleroderma-specific antibodies: centromeres, topoisomerase I, RNA polymerases I or III, Th
  3.  antibodies assoc. w/ scleroderma overlap: U1-RNP, U2-RNP, U3-RNP, U5-RNP, Pm-Scl,Ku
  4. signal recognition particle antibody
  5. antibody against nucleoporins

SLE-DM OVERLAP VS MIXED CONNECTIVE TISSUE DISEASE

Of all the connective tissue diseases, DM most commonly overlap with scleroderma.  Scleroderma was also considered as a component of the overlap because of the skin tightening (as described by the patient and the medical team) and dysphagia; however it was not considered because of the absence of the expected increased deposition of collagen in the skin biopsy (which is highly suggestive for scleroderma). Had it remained a consideration, the constellation of symptoms of SLE, DM/PM and Scleroderma will point to Multiple Connective Tissue Disease (MCTD) as a major impression. The clinical overlap features of MCTD seldom occur concurrently and they develop sequentially over the course of months or years (14).

ASSOCIATED ANTIPHOSPHOLIPID SYNDROME

Theoretically, as DM has been reported in association with SLE, and antiphospholipid syndrome (APS) is commonly found in SLE, APS and DM may present in the same patient as part of lupus overlap. A few cases reported an association of DM alone with APS (16).  The presence of antiphospholipid antibody (aPL) was found to be an independent risk factor for ischemic stroke, similar in magnitude to that of diabetes or hypertension in the elderly population without SLE. In a series of young stroke patients, the prevalence of aPL ranges from 18 to 46% (16). In our case, the history of abortion (although not multiple) and cerebrovascular disease suggested the possibility of a concomitant antiphospholipid antibody syndrome. However, APS work-ups were negative. Perches et.al. demonstrated the sensitivities, specificities, and negative predictive values of IgM ACL (92%, 1.2%, 33.3%), IgG ACL (40%, 82.5%, 81.4%) and lupus anticoagulant (12%, 97.5%, 78.2%) using DVVRT and KCT for the diagnosis of APS (20). Hence, in our case, an associated APS is unlikely.

 DM  AND MALIGNANCY

An association between DM and malignancies was observed in early case reports (8). Rates of malignancy in patients with DM (and PM) vary from 3% to 35.7% depending on the study group (15). DM has been found to be a paraneoplastic phenomenon in 15% to 30% of adult patients (9, 11, 12). The most common forms of malignancy associated with DM are ovarian cancer, breast cancer, melanoma, colon cancer and non-Hodgkin’s lymphoma (13). This association corresponds most closely with the dermatologic manifestations, as  in patients with DM who do not have muscle disease. The incidence, however, of malignancy is lower in patients with the muscle disease alone (i.e., PM). The degree of muscle involvement did not correlate with rates of DM-associated malignancy (9). We have not found any study directly linking SLE-DM overlap syndrome with malignancy. However, it is prudent to consider this association of DM (alone) with malignancies in patients with DM-associated overlap syndrome, as in our case.

TREATMENT AND PROGNOSIS

The rational management of overlap syndromes is confounded by the absence of controlled trials. Recommendations for management are based on conventional treatments for SLE, PM, DM, rheumatoid arthritis, and scleroderma (14).

Generally, DM responds to steroid therapy (with 87% response rate). Treatment is initiated with high-dose hydrocortisone or prednisone (10mg/kg). However, the cutaneous manifestations may fail to respond to immunosuppressive treatment, despite improvement in muscle symptoms. It is also important to note that cutaneous disease in DM does not always parallel muscle disease in its onset, activity, or response to therapy (10). Among those with associated malignancy, the rash and symptoms may clear following resection of the tumor (8). 

Mortality of DM has varied from 8.9% to 52%. However, the wide range may be a result of a disease with variable manifestations. Duration of follow-up can also affect the perceived prognosis. One-year survival has varied from 83% to 95%, whereas 5-year survival has ranged from 63% to 95%, with 9-year or greater survival rates ranging from 53% to 100%, depending on the disease subtype (15). The worst prognosis is seen in cancer-associated DM. The underlying malignancy, not the DM, accounts for the poor outcome (15).

Management of the SLE component requires a comprehensive assessment of disease activity and target organ damage. The presence or absence of organ involvement determines the treatment regimen (14). NSAIDs, antimalarials, glucocorticoids, and, in severe, refractory cases, immunosuppressive agents (azathioprine, mycophenolate mofetil, cyclophosphamide,  methotrexate) are used in the treatment of SLE patients. Most experts agree that the treatment of moderate-to-severe SLE consists of a period of intensive immunosuppressive therapy (induction therapy) followed by a longer period of less intensive maintenance therapy.

Myositis overlap syndromes (vs DM alone) were almost always responsive to high dose prednisone alone (89-100% vs 87% response rate) (17). Markers for corticosteroid responsiveness are autoantibodies to U1-RNP, Pm-Scl, or Ku, whereas markers for treatment-resistance are antisynthetase, SRP, and nucleoporin autoantibodies (17). Furthermore, antibodies to Ro and Ro52 were independently associated with responsiveness of myositis to prednisone alone. The opposite was observed for anti-Jo1 (18).

The associated malignant neoplasms are diagnosed at or before the time of diagnosis of DM (8). Therefore, early cancer detection and treatment must be done. It is imperative to screen for tumors in patients with dermatomyositis, even as part of an overlap syndrome, at the time of diagnosis and at relapse, particularly if the symptoms do not respond to conventional immunosuppressive treatment. Though age over 50 years old put patients at greater risk for cancer-association, the incidence of cancer declines steadily with the duration of PM/DM. The risk of cancer is increased approximately sixfold during the first year, but is lower during the second year, with no significant excesses in subsequent years of follow-up (8). Therefore among long-term survivors of PM/DM, there is little evidence to warrant extensive preventive and screening measures after 2 years. Tumors may appear at any site, but significantly more in the lung, ovary, breast, lymphatic and hematopoietic systems, and nasopharyngeal areas. In 30% of patients the tumor appeared first, and symptoms of DM subsequently appeared, with a mean interval of 16 months (8). Recurrence of dermatomyositis may indicate the occurrence of a second primary malignancy or recurrent cancer. The screening for malignancies should include a careful clinical examination, routine blood tests, chest radiograph, and mammography and a gynecologic examination for women. If any abnormalities are found, these should guide a more thorough investigation for malignancies. (14). In Asians, nasopharyngeal carcinoma is common, and a careful examination of ears, nose and throat is indicated. (13).

FINAL DIAGNOSIS

Overlap dermatomyositis with systemic lupus erythematosus features; invasive ductal carcinoma of left breast; previous cerebrovascular disease, left cerebellar infarct.

REFERENCES:

  1. Hochberg, et al, Rheumatology 3rd edition, 2003
  2. Radulescu D,et al, A Rare Case of Systemic Autoimmune Disease with Intricate Features of Systemic sclerosis, Lupus, Polymyosistis and Rheumatoid arthritis: Overlap syndrome or Mixed connecteive tissue Disease, Acta Reumatologica Portugal 2007;32:292-297
  3. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [letter]. Arthritis Rheum 1997;40:1725
  4. Tan EM, et al. The 1982 Revised Criteria for the Classification of Systemic Lupus Erythematosus. Arthritis Rheum 1982; 25:1271-1277.
  5. Wallace, D., et al, Dubois’ Lupus Erythematosus  7th edition
  6. Takken T., et al. The physiological and physical determinants of functional ability measures in children with juvenile dermatomyositis. Rheumatology (Oxford) 2003; 42:158-62
  7. Tanimoto K, et al, Classification criteria for polymyositis and dermatomyositisJournal of Rheumatology 1995; April 22 (4); 668-674  Abstract
  8. Habif: Clinical Dermatology, 4th edition, Mosby 2004
  9. Goyal S., et al, Paraneoplastic amyopathic dermatomyositis associated with breast cancer recurrence Journal of the American Academy of Dermatology - Volume 41, Issue 5 (November 1999).
  10. Klein, R., et al, Number, characteristics, and classification of patients with dermatomyositis seen by dermatology and rheumatology departments at a large tertiary medical center. Journal  of the American Academy  of Dermatology.2007;08:24
  11. Callen JP, Hyla JF, Bole GG, Kay DR. The Relationship of Dermatomyositis and Polymyositis to Internal Malignancy. Archives of Dermatology1980;116:295-8.
  12. Barnes BE. Dermatomyositis  and Malignancy. Annals of  Internal  Medicine 1976;84:68-76.
  13. Kasper,et al, Harrison’s Principles of Internal Medicine 17th edition
  14. Firestein: Kelly’s Textbook of Rheumatology, 8th ed.
  15. Iorizzo III, L et al, The treatment and prognosis of dermatomyositis: An updated review, Journal  of the American  Academy of Dermatol ogy 2008;59:99-112
  16. Sherer,Y.,et al,  Dermatomyositis and polymyositis associated with the antiphospholipid syndrome-a novel overlap syndrome, Lupus 2000;9: 42-46
  17. Troyanov Y,  et al: Novel classification of idiopathic inflammatory myopathies based on overlap syndrome features and autoantibodies: Analysis of 100 French Canadian patients. Medicine(Baltimore) 84:231-249, 2005.
  18. Koenig ,M. et al, Heterogeneity of autoantibodies in 100 patients with autoimmune myositis: insights into clinical features and outcome, Arthritis Research & Therapy 2007;9 (4):R78
  19. http://www.neuropathologyweb.org/test12-13/12-13test.html

Perches, et al, Evaluation of antiphospholipid antibodies testing for the diagnosis of antiphospholipid syndrome, Revista Brasileira de Reumatologia 2009; 49 (3)

APPENDIX A

American College of Rheumatology Revised Classification Criteria for Systemic Lupus Erythematosus

If ≥ 4 of these criteria, well documented, are present at any time in a patient’s history, the diagnosis is likely to be SLE. Specificity 95%, Sensitivity 75%

Criteria

Definition

Malar rash

Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds

Discoid rash

Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring occurs in older lesions

Photosensitivity

Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation

Oral ulcers

Oral or nasopharyngeal ulceration, usually painless, observed by a physician

Arthritis

Nonerosive arthritis involving two or more peripheral joints, characterized by tenderness, swelling, or effusion

Serositis

  

a.   

Pleuritis—convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion or

  

b.   

Pericarditis—documented by ECG or rub or evidence of pericardial effusion

Renal disorder

  

a.   

Persistent proteinuria >0.5 g/day >3+ if quantitation is not performed or

  

b.   

Cellular casts—may be red blood cell, hemoglobin, granular tubular, or mixed

Neurologic disorder

  

a.   

Seizures—in the absence of offending drugs or known metabolic derangements (e.g., uremia, acidosis, or electrolyte imbalance) or

  

b.   

Psychosis—in the absence of offending drugs or known metabolic derangements (e.g., uremia, acidosis, or electrolyte imbalance)

Hematologic disorder

  

a.   

Hemolytic anemia with reticulocytosis, or

  

b.   

Leukopenia—<4000/mm3, or

  

c.   

Lymphopenia—<1500/mm3, or

  

d.   

Thrombocytopenia—<100,000/mm3 in the absence of offending drugs

Immunologic disorder

  

a.   

Anti-DNA—antibody to native DNA in abnormal titer, or

  

b.   

Anti-Sm—presence of antibody to Sm nuclear antigen, or

  

c.   

Positive finding of antiphospholipid antibodies based on (1) abnormal serum concentration of IgG or IgM anticardiolipin antibodies, (2) positive test result for lupus anticoagulant using a standard method, or (3) false-positive serologic test for syphilis known to be positive for at least 6 mo and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test

ANA

Abnormal titer of ANA by immunofluorescence or equivalent assay at any point in time and in the absence of drugs known to be associated with drug-induced lupus syndrome

Adapted from Hochberg MC, et al, Rheumatoloogy 3rd edition 2003

APPENDIX B

Bohan and Peter Criteria for Polymyositis and Dermatomyositis

First exclude all other myopathies

Symmetric proximal muscle weakness

Increase in serum muscle enzymes, such as CK, AST, ALT, aldolase, and LDH

Abnormal electromyographic findings, such as short, small, polyphasic motor units; fibrillations; positive sharp waves; insertional irritability; and bizarre high-frequency repetitive discharges

Abnormal muscle biopsy findings, such as mononuclear infiltration, regeneration, degeneration, and necrosis

Skin rashes, such as the heliotrope rash, Gottron's sign, and Gottron's papules

DIAGNOSIS:

Definite myositis: 4 criteria (without the rash) for PM; 3 or 4 criteria (plus the rash) for DM

Probable myositis: 3 criteria (without the rash) for PM; 2 criteria (plus the rash) for DM

Possible myositis: 2 criteria (without the rash) for PM; 1 criterion (plus the rash) for DM

ALT, alanine transaminase; AST, aspartate transaminase; CK, creatine kinase; LDH, lactate dehydrogenase.

APPENDIX C

Criteria for Classifiation of Dermatomyositis and Polymyositis ( Tanimoto 1995)

proximal muscle weakness

muscle grasping and spontaneous pain

nondestructive arthritis or arthralgia

elevated CK or aldolase level

presence of systemic inflammatory signs

myogenic changes on EMG

positive and anti Jo-1 antibody

pathologic findings compatible with inflammatory myositis

Skin lesions such as heliotrope rash, Gottron's sign and erythema or purpura on the   extensor surfaces of the extremity joints

DM: if with one of 3 skin lesion items and at least 4 other items; with sensitivity 94.1%.

PM: if with at least 4 items other than skin lesion items; sensitivity 98.9%.

Specificity of DM and PM is 95.2%.

APPENDIX D

Classification for Inflammatory Myopathies

Descriptions

Pure polymyositis (PM)

Pure dermatomyositis (DM)

Overlap myositis (OM): myositis with at least one clinical overlap feature or an overlap autoantibody

Cancer-associated myositis (CAM): clinical paraneoplastic features without an overlap autoantibody or anti–Mi-2

     Bohan and Peter Definition of Myositis

1. Symmetric proximal muscle weakness

2. Elevation of serum skeletal muscle enzymes

3. Electromyographic triad of short, small, polyphasic motor unit potentials; fibrillations, positive sharp waves, and insertional irritability; and bizarre, high-frequency repetitive discharges

4. Muscle biopsy abnormalities of degeneration, regeneration, necrosis, phagocytosis, and interstitial mononuclear infiltrate

5. Typical skin rash of DM, including heliotrope rash, Gottron's sign, and Gottron's papules

Definite myositis: 4 criteria (without the rash) for PM; 3 or 4 criteria (plus the rash) for DM

Probable myositis: 3 criteria (without the rash) for PM; 2 criteria (plus the rash) for DM

Possible myositis: 2 criteria (without the rash) for PM; 1 criterion (plus the rash) for DM

     Definition of Clinical Overlap Features

Inflammatory myopathy plus at least one or more of the following clinical findings: polyarthritis, Raynaud's phenomenon, sclerodactyly, scleroderma proximal to metacarpophalangeal joints, typical SSc-type calcinosis in the fingers, lower esophageal or small-bowel hypomotility, Dlco lower than 70% of normal predicted value, interstitial lung disease on chest radiograph or computed tomography scan, discoid lupus, anti- native DNA antibodies plus hypocomplementemia, 4 or more of 11 American College of Rheumatology criteria for systemic lupus erythematosus, antiphospholipid syndrome

Definition of Overlap Autoantibodies

Antisynthetases (Jo-1, PL-7, PL-12, OJ, EJ, KS), scleroderma-associated autoantibodies (scleroderma-specific antibodies: centromeres, topoisomerase I, RNA polymerases I or III, Th; and antibodies associated with scleroderma overlap: U1-RNP, U2-RNP, U3-RNP, U5-RNP, Pm-Scl, Ku, and other autoantibodies (signal recognition particle, nucleoporins)

Definition of Clinical Paraneoplastic Features

Cancer within 3 yr of myositis diagnosis, plus absence of multiple clinical overlap features; plus, if cancer was cured, myositis was cured as well

Adapted from Troyanov Y, Targoff IN, Tremblay JL, et al: Novel classification of idiopathic inflammatory myopathies based on overlap syndrome features and autoantibodies: Analysis of 100 French Canadian patients. Medicine (Baltimore) 84:231-249, 2005.