A 17-year-old girl with facial edema and weakness

A previously healthy 17-year-old adolescent initially presented to her dentist with right-sided facial swelling for 2 weeks. There was concern for an infected tooth which was extracted. Nevertheless, progression of facial edema ensued with recurrent fevers requiring admission to a community hospital where swabs of the tooth socket failed to identify a pathogen. Despite treatment with five suitable intravenous antibiotics over 3 weeks, she failed to improve. This resulted in transfer to our paediatric hospital. On admission, she reported dysphagia, weight loss and fatigue. Physical examination was significant for asymmetrical face and neck swelling with periorbital edema, periodontal gingival erythema and abnormal nail fold capillary pattern on capillaroscopy. She had a hoarse voice and significantly reduced proximal muscle strength. Oxford scale manual muscle testing was 2/5 proximally and 4/5 distally. There were no apparent rashes (Figure 1). Laboratory investigations are shown in Table 1. Head and neck magnetic resonance imaging revealed significant edema of the facial, neck and retropharyngeal muscles without venous thrombosis. Magnetic resonance imaging of the pelvic and shoulder girdles confirmed extensive subcutaneous and proximal muscle edema with deep and superficial fasciitis. Video fluoroscopy demonstrated weak pharyngeal and esophageal muscles. A muscle biopsy revealed the diagnosis.

Figure 1.

Bilateral face swelling (including upper eyelids).

Table 1.

Pertinent laboratory investigations

Investigation	Patient	Normal range
White blood cell count (×109/L)	3.9	4.0–11.0
Lymphocytes (×109/L)	0.7	1.2–5.2
Hemoglobin (g/L)	107	120–160
Platelets (×109/L)	124	140–150
Alanine transaminase (U/L)	245	<17
Aspartate transaminase (U/L)	302	<28
Creatine kinase (U/L)	4265	53–310
Lactate dehydrogenase (U/L)	578	0–184
Albumin (g/L)	36	37–52
TSH (mIU/L)	5.8	0.34–5.6
C3/C4 (g/L)	0.92/0.22	7.9–1.5/0.17–0.47
IgG/IgA/IgM (g/L)	7.8/0.92/1.55	6.8–15.3/0.94–4.67/0.44–1.68
Urinalysis	Normal (negative protein)	Normal
Echocardiogram heart	Normal	Normal
dsDNA, ENA, SCL 70	Negative	Negative
Antiphospholipid Ab	Negative	Negative

ENA, extractable nuclear antigen antibodies; TSH, thyroid-stimulating hormone. Infectious work-up (all negative): Blood cultures, nasal pharyngeal aspirate for respiratory viruses, purified protein derivative skin test, Human immunodeficiency virus, Antistreptolysin O titer, Anti-Deoxyrubnocluease B, titers, as well as serologies for Toxoplasma, Varicella Zoster Virus, Trichinella, Cytomegalovirus and Ebstein-Barr Virus.

DISCUSSION

A right rectus femoris muscle biopsy revealed perifascicular inflammation and atrophy with tubuloreticular inclusions on electron microscopy, consistent with dermatomyositis. High-dose methylprednisolone and intravenous immunoglobulin (IVIG) were initiated. Her clinical course was complicated by macrophage activation syndrome (MAS), prompting initiation of intravenous cyclosporine therapy. MAS features included platelets 41 × 109/L, hemoglobin 66 g/L, fibrinogen 1.16 g/L, ferritin 577 µg/L, albumin 28 g/L, D-dimer 2.14 µg/ml and a bone marrow biopsy consistent with hemophagocytosis. On this regimen her muscle strength and gingival and nail fold capillary changes gradually improved. Within 5 weeks of admission, muscle enzymes and MAS-associated laboratories normalized. Once video fluoroscopy demonstrated sufficient airway protective mechanisms during swallowing and she was slowly introduced to suitable oral meals. A team of allied health professionals provided comprehensive rehabilitation. She was discharged on high dose oral prednisone and cyclosporine with IVIG biweekly. At 1-year postdiagnosis, she was doing well on cyclosporine, low-dose prednisone and IVIG every 3 weeks.

Our patient met histologic criteria for juvenile dermatomyositis. Classically, this disease presents acutely or insidiously with malaise, fatigability, symmetrical proximal muscle weakness and particular cutaneous features (Table 2). Histologic features include chronic dermatologic and muscle inflammation with evidence of perifasicular lymphocytic cell infiltration. Onset is typically at 5 to 14 years of age with female predominance. Facial edema has been reported as the dominant clinical feature in only a few published adult studies and one paediatric case report (1). In the latter, periorbital edema was the sole cutaneous finding at disease onset but eventually more typical skin findings emerged. Our patient never developed a characteristic rash, yet her periungual erythema and nail fold capillary changes pointed towards a cutaneous small vessel vasculopathy. Her muscle biopsy results were classic for dermatomyositis, allowing definite differentiation from polymyositis. Further testing revealed nuclear matrix protein 2 antibodies, which are usually associated with a dermatomyositis phenotype characterized by less severe skin disease. She later developed calcinosis at the biopsy site, which is typical of this subtype.

Table 2.

Criteria for a diagnosis of Juvenile dermatomyositis and polymyositis

3/5 findings indicates probable myositis 4/5 findings indicates definite myositis Exclusion of all other conditions in the differential diagnosis Cutaneous changes are required for the diagnosis of dermatomyositis

1. Symmetric weakness of the proximal musculature

2. Characteristic cutaneous changes consisting of heliotrope discoloration of the eyelids, which may be accompanied by periorbital edema and/or erythematous papules over the extensor surfaces of joings, including the dorsal aspects of the metacarpophalangeal and proximal interphalangeal joints, elbows, knees, or ankles (i.e., Gottron papules)

3. Elevation of the serum level of one or more of the following skeletal muscle enzymes: creatine kinase, aspartate aminotransferase, lactate dehydrogenase, and aldolase

4. Electromyographic demonstration of the characteristics of myopathy and denervation, including the triad of polyphasic, short, small motor-unit potentials; fibrillations, positive sharp waves, increased insertional irritability; and high-frequency repetitive changes

5. Muscle biopsy documenting histological evidence of necrosis; fiber size variation, particularly perifascicular atrophy; degeneration and regenerations; and a mononuclear inflammatory infiltrate, most often in a perivascular distribution

Data taken from ref. (6).

Differential diagnosis of facial edema is extensive and may include infections (especially trichinosis), hereditary angiedema, hypothyroidism, cardiac disease, nephrotic syndrome, malnutrition, hypersensitivity reaction (including allergic angiedema), deep vein thrombosis, lymphatic obstruction, malignancy and certain rheumatic conditions, such as dermatomyositis and systemic lupus erythematous. These were ruled out in our patient (Table 1).

Early diagnosis of dermatomyositis is critical to implement appropriate treatment and prevent disease-related fatality. Death from dermatomyositis in the paediatric population is rare, but our patient presented with multiple risk factors for increased mortality, including the rapid onset of severe weakness, distal muscle involvement, weight loss, older age at disease onset and the presence of hoarseness and significant dysphagia (2). Combined treatment with steroids and either cyclosporine or methotrexate has been shown in a randomized control trial to be more effective than prednisone alone (3). Supportive treatment is essential with ongoing airway and swallowing assessments, as well as total parenteral nutrition.

There were concerns about modest cytopenias at disease onset prompting a workup for underlying malignancies, which proved negative. Cancer-associated dermatomyositis is very rare in children whereas leukemia, lymphoma and solid organ-tumours are frequently associated with adult onset disease. We also searched for MAS. The hallmark of this life-threatening condition is uncontrolled activation and proliferation of lymphocytes and macrophages leading to hypersecretion of proinflammatory cytokines. The most common associated rheumatic condition is systemic juvenile idiopathic arthritis whereas it is a rare feature of dermatomyositis (4). MAS criteria are listed in Table 3 (5). Her prognosis remains guarded related to the requirement of long-term immunosuppressive treatment for chronic dermatomyositis and the possibility of MAS recurrences.

Table 3.

Criteria for macrophage activation syndrome: At least 2 lab or 1 clinical + 1 lab

Clinical

1. Nonremitting high fever

2. Hepatomegaly

3. Splenomegaly

4. Lymphadenopathy

5. Hemorrhages

6. Central nervous system dysfunction

Laboratory (Lab)

1. Cytopenia

2. Abnormal liver function tests

3. Coagulopathy

4. Decreased erythrocyte sedimentation rate

5. Hypertriglyceridemia

6. Hyponatremia

7. Hypoalbuminemia

8. Hyperferritinemia

9. Histopathologic: Macrophage hemophagocytosis in bone marrow

Data taken from ref. (5).

CLINICAL PEARLS

1. The differential diagnosis of a patient presenting with localized facial edema includes certain rheumatic conditions, such as dermatomyositis and systemic lupus erythematous. Once infectious aetiologies have been excluded, there should be a high index of suspicion for systemic inflammatory diseases.

2. Early diagnosis of dermatomyositis and the rapid administration of high dose glucocorticoids in combination with cyclosporine/methotrexate is the most important factor in altering disease prognosis.

3. Juvenile dermatomyositis may present with life-threatening complications (airway compromise, aspiration, and macrophage activation syndrome), which need to be recognized and treated promptly.

Funding Source: No external funding was obtained.

Financial Disclosure: The authors have no financial relationships relevant to this article to disclose.

Conflict of Interest: The authors report no conflicts of interest.

Area of specialization: Rheumatology.