1. Overview of Juvenile Dermatomyositis
Pediatric Rheumatology
Red Team Resident
Teaching Series

2. What is Juvenile Dermatomyositis?
“A multisystem disease of uncertain origin that results in chronic inflammation of striated muscle and skin.” (Cassidy and Petty, 2011)
A rare pediatric autoimmune disease, but the most common inflammatory myopathy in children
Average annual incidence rate: 3.2 cases per 1 million children (Mendez, EP, et al. 2003)
16-20% of all dermatomyositis patients have onset in childhood
Girls > boys (2.2:1)
Peak age of onset: 7.6 years old, peak range: 5-14 years of age
No difference in incidence in different ethnicities

3. What is Juvenile Dermatomyositis?
Systemic small vessel vasculopathy
Mainly muscle and skin involvement, but can involve other organ systems
Presentation: insidious onset malaise, fever, fatigue, rash, muscle weakness/pain
Don’t always have skin AND muscle manifestations at the same time
Amyopathic JDM = JDM without evidence of muscle involvement

4. Differential Diagnosis of Juvenile Idiopathic Inflammatory Myopathies
Feldman et al, Lancet 2008; 371,

5. JDM - Etiology & Pathogenesis
Cause unknown
Likely autoimmune angiopathy
Environmental and genetic factors implicated
A history of infection prior to onset is common
65- 70% of patients have a history of a significant infection during the three months prior to first onset of symptoms
Proposed triggers include various infectious agents, vaccines, medications, UV light
Cellular and humoral immunity implicated
Complement-mediated injury important
Innate immune response: type I interferons and dendritic cells

6. Cellular and Humoral Immunity
Autoimmunity
~70-80% JDM patients have positive ANA
~10% children have classic myositis specific antibodies (MSA) compared to >50% adults
Some auto-antibodies that you might see positive in these patients: anti-Jo1, anti-SSA, anti-SSB, anti-topoisomerase, anti-U1RNP
Abnormalities of cell-mediated immunity
MHC class I antigens strongly expressed by muscle cells of JDM patients but not normal controls
Association with immunodeficiency
Occurrence in children with hypogammaglobulinemia, selective IgA deficiency, & C2 deficiency

7. Clinical Features of JDM Patients
Constitutional
Fever: 16-65%
Adenopathy: 20%
Lethargy: 10%
Musculoskeletal
Weakness: 95%
Myalgia or arthralgia: 25-73%
Arthritis: 23-58%
Contractures: 26-27%
Raynaud’s disease: 9-14%
Cutaneous
Gottron’s papules: %
Heliotrope rash: %
Nailfold capillary changes: 91%
Malar or facial rash: 42-73%
Mouth ulcers: 35%
Skin ulcers: 23-30%
Limb edema: 11-32%
Calcinosis: 6-30%
Lipodystrophy: 10-14%
Pulmonary
Dyspnea: 7-43%
Gastrointestinal
Dysphonia or dysphagia: 18-44%
Gastrointestinal symptoms: 22-37%
Feldman et al, Lancet 2008; 371,

8. Dermatomyositis – other organ involvement
Gastrointestinal vasculitis- gut wall perforation
Arthritis - common but usually early and mild, non-erosive
Cardiac - inflammation, fibrosis, conduction defects
Renal - glomerular hypercellularity
Pulmonary - fibrosis, pneumothorax
Central nervous system - behavior changes, seizures
Alopecia
Eyes - exudative vasculitis of retina
Derm – calcinosis, subcutaneous nodules, ulcerations
Lipodystrophy

9. The Pictures of Juvenile Dermatomyositis
Heliotrope Rash with periorbital edema
Malar rash
Rash on extensor surfaces
Gottron’s Papules
V Sign
Shawl Sign
Calcinoses

10. Heliotrope: The flower for which the rash is named!

11. Periorbital edema and heliotrope rash
The heliotrope rash occur over the upper eyelids and is violaceous, reddish-purple in coloration (see last slide). It is often associated with periorbital edema, and is often accompanied by a malar rash (see next slide). It is one of the most common rashes seen in JDM.

12. Facial and extremity rash
The facial rash of JDM appears in a malar-distribution (bilateral cheeks, extending across the nasal bridge, sparing the nasolabial folds), similar to the malar rash seen in lupus but usually less well-demarcated. The chin and forehead can also be involved. This tends to be a photosensitive rash. This patient also has rash on her bilateral elbows, consistent with Gottron’s papules (see next slide).

13. Gottron’s papules
Gottron’s papules are shiny, erythematous, scaly plaques seen in a symmetrical distribution on the extensor surfaces of the upper and lower extremities (often over the MCPs, PIPs, and DIPs of the hands, also occur on the elbows, knees, and sometimes on the malleoli of the ankles). They can start initially as flat erythematous lesions. It is one of the most common rashes seen in JDM. Note also the erythema around the nailbeds, reflecting nailbed capillary abnormalities, another common finding (see next slide).

14. Nailbed Capillary Abnormalities
A common finding in JDM, this reflects active vasculitis of the nailbed capillaries. Upper left, a normal nailfold capillary pattern. Upper right, shows dilation of capillary loops, with loss of surrounding loop structures (“drop-out”). Lower right, dilated capillary loops are present with areas of arborized clusters of loops. Lower left, dilated and prominent capillary loops.

15. Other Skin Manifestations
Photosensitive rash can also occur on the chest, neck, extremities, scalp (this is the V-sign and shawl sign seen on Slide #7)
May evolve into poikiloderma (hyper or hypopigmentation with atrophy and telangiectasia)
Mechanic’s hands
Pruritis, psoriasiform scalp dermatitis
Poikiloderma: Confluent violaceous papules with mottled dyspigmentation and telangiectasias
Mechanic’s hands: Scaly, fissured, hyperkeratotic skin suggestive of manual labor

16. Other Skin Manifestations
Lipodystrophy (below): reported in ~ 20% of JDM patients . Can be generalized, partial, or localized; characterized by a progressive, slow, and symmetrical loss of subcutaneous fatty tissue, which is often most noticeable over the face and the limbs.
Calcinosis (above): seen in 12-43% of JDM patients, this tends to be a sign of chronic disease and rarely presents at diagnosis. These are calcium salt deposits from muscle inflammation that deposit in subcutaneous tissues, often over pressure-bearing surfaces. These can be superficial and can open to the environment, expressing calcium material, and can become superinfected. These can self-resolve, lessen in size, or remain unchanged. Trauma can be associated with formation. If they occur over joints they can cause joint contractures.

17. Muscle Weakness
Probably affects all muscle groups, but proximal > distal
Most obvious in limb-girdle, neck flexors, and trunk muscles
May be tender, edematous, indurated
Respiratory weakness
In one report, ~ ¼ patients had involvement of pharyngeal, hypopharyngeal, and palatal muscles
Difficulty swallowing, dysphonia, nasal speech, regurgitation of liquids through nose
Aspiration risk
May have Gowers’ or Trendelenberg’s sign

18. Gowers’ Sign
Trendelenberg’s Sign

19. How is it diagnosed? Symmetrical weakness of the proximal musculature
Characteristic cutaneous changes consisting of heliotrope discoloration of the eyelids, which may be accompanied by periorbital edema and erythematous papules over the extensor surfaces of joints, including the dorsal aspects of the metacarpophalangeal and proximal interphalangeal joints, elbows, knees, or ankles (i.e. Gottron papules)
Elevation of the serum level of one or more of the following skeletal muscle enzymes: CK, AST, LDH, Aldolase
EMG demonstration of the characteristics of myopathy and denervation
Muscle biopsy documenting histological evidence of necrosis
*** MRI of thigh muscles is preferred modality to establish presence of myositis in many centers (symmetrical muscle edema on fat-suppressed T2-weighted or STIR sequences), but is not specific for myositis as edema associated with other myopathies can appear similar on MRI.
Definite JDM: rash + 3 other criteria
Probable JDM: rash + 2 other criteria
Criteria from Bohan and Peter: Polymyositis and dermatomyositis, N Engl J Med 292: , , 1975.

20. Revisiting the Criteria for JDM
Although criteria used for JDM, sensitivity and specificity not validated in children (estimated 45-90% & 90%)
For JDM diagnosis, require rash and 2 of 4 other criteria for diagnosis
Most institutions don’t do EMG or biopsy if diagnosis is clear.
MRI often being used in difficult cases, less painful and invasive than EMG or biopsy

21. Typical Laboratory Findings:
Elevated muscle enzymes: Creatinine Kinase, Aldolase, LDH, AST, ALT
Elevated inflammatory markers: ESR, CRP
May have lymphopenia, but leukopenia and anemia are uncommon at onset of disease
Positive ANA in ~ 70-80% of patients
Other autoantibodies commonly tested that might be positive in JDM patients:
Anti-Jo1 – 2-5%
Anti-Ro (SSA) – 2-8%
Anti-La (SSB) – 1%
Anti-U1RNP – 5-6%

22. So what happens to these kids?
Prior to steroids: 1/3 self-resolved, 1/3 would resolve but develop significant morbidity, 1/3 would die
Morbidity and mortality rates have improved with the use of steroids and DMARDs
Mortality < 3%, 28-41% with functional disability, 37-41% with monocyclical course
Some patients do continue to have persistent chronic skin changes

23. Treatment: First line: Additional treatment options:
Prednisone/Methylprednisone
Methotrexate
Additional treatment options:
IVIG
Cyclosporine
Tacrolimus
Mycophenolate Mofetil
Azathioprine
Cyclophosphamide
Adjunctive therapies:
Physical therapy
Hydroxycholorquine
Sun protection
Calcium/Vitamin D

24. Board Review Question
A 7 year old girl has a 2 month history of generalized weakness and a rash. Findings on exam include a violaceous discoloration of the malar regions, erythematous papules over the interphalangeal joints, and nailfold telangiectasias. Proximal muscle strength is 3/5. Of the following, the MOST appropriate intial step in evaluating this patient’s symptoms is to obtain a(n): a. antinuclear antibody titer b. creatine kinase concentration c. electromyogram d. magnetic resonance image of muscle e. muscle biopsy