A previously healthy 13-year-old girl presented with a 6-week history of fatigue, muscle weakness, sore throat, and upper and lower extremity edema. A rash along the elbows and submental and malar area was also reported. During this interval, the patient was treated by her primary care physician for streptococcal pharyngitis, presumed bronchitis, and otitis media with consecutive courses of amoxicillin, cephalexin, and azithromycin without improvement of symptoms. On examination, the patient was noted to have a mild erythematous rash in the submental region, bilateral raised erythematous papules overlying the metacarpal and interphalangeal joints (Gottron’s papules), 3/5 muscle strength in the lower extremities, 1+ non-pitting edema in the upper extremities, and 2+ pitting edema in the lower extremities.
Two days after being admitted for further work-up, the patient was seen by the ophthalmology department after complaining of gradually worsening vision in both eyes during the prior 2 weeks. Her visual acuity on initial examination was noted to be 20/80 in the right eye and 20/60 in the left eye. Her dilated fundus examination showed multiple diffuse exudates in both eyes. The remainder of her ocular examination did not show any additional findings consistent with vasculitic changes such as conjunctival injection, keratic precipitates, anterior chamber or vitreous cell, or vascular sheathing.
Initially, and throughout her hospital course, the patient’s blood pressure and blood sugars were within normal limits. Laboratory work showed a creatine phosphokinase level of 11,501 units/L (normal: 50 to 240 units/L), a lactate dehydrogenase level of 2,873 units/L (normal: 370 to 645 units/L), and negative autoimmune antibodies (ANA, Jo1, SCL-70, RNP, SSA, SSB, Smith), and a bone marrow biopsy was negative. A muscle biopsy taken of the left vastus lateralis showed inflammation suggestive of dermatomyositis.
Initial treatment consisted of one 80-mg dose (2 g/kg) of intravenous immunoglobulin (IVIG) infused over 12 hours and an intravenous methylprednisolone 30 mg/kg/day (1 g maximum) pulse for 3 consecutive days, and the patient showed clinical improvement with each successive dose. The patient was then discharged home with oral prednisolone 21 mg daily and planned weekly pulses of intravenous methylprednisolone and biweekly IVIG doses in the hopes of continued improvement.
On the next ophthalmic examination 3 days after discharge (seventh day after initial treatment), her dilated fundus examination showed diffuse cotton wool spots bilaterally with visual acuity reduced to 20/150 in the right eye and 20/125 in the left eye. The following day (eighth day after initial treatment), because of the ophthalmic findings, a pulse intravenous cyclophosphamide 750 mg/m2 (980 mg) was started by the rheumatology team with concurrent mesna treatment and a slow steroid taper was begun. Over the course of the next several months, as the creatine phosphokinase level continued a downward trend to the range of 50 to 100 units/L, the patient’s diffuse cotton wool spots slowly resolved and visual acuity improved to 20/20 with concurrent improvement in her systemic complaints. No systemic or ocular complications of the treatment were noted.
A previously healthy 9-year-old girl with a strong family history of autoimmune disease presented with a 3-week history of subjective fever, rash, and progressive lower extremity weakness. She was initially treated by her primary care physician with diphenhydramine, amoxicillin, and a 5-day course of prednisolone without resolution of symptoms. On examination, she was noted to have an erythematous rash along her chest extending up her neck, a heliotrope rash, and severe proximal lower extremity pain and weakness rendering her unable to stand from a seated position or walk for prolonged periods without assistance. In addition, she had velopharyngeal weakness with dysphagia and difficulty with speaking.
Her autoimmune laboratory tests (including ANA, SSA, SSB, Smith, RNP, Jo1, SCL-70, and double-stranded DNA antibodies) were negative, creatine phosphokinase level was 12,123 units/L (normal: 50 to 240 units/L), lactate dehydrogenase level was 2,986 units/L (normal: 370 to 645 units/L), aldolase level was 46.5 units/L (normal: < 14.5 units/L), and erythrocyte sedimentation rate was 30 mm/hr (normal: 0 to 13 mm/hr). Although a muscle biopsy of the left vastus lateralis showed a lack of significant inflammatory cells, magnetic resonance imaging of the lower extremities showed significant edema and findings consistent with severe myositis. Therefore, the clinical suspicion for juvenile dermatomyositis was high because it was possible that the biopsy did not obtain tissue that was affected by the disease. Pulse intravenous methylprednisolone 30 mg/kg (maximum 1 g) was started and given every other day for three doses, after which the patient was transitioned to oral prednisolone at 2 mg/kg divided twice daily.
An ophthalmology consultation was ordered several days after admission due to the patient’s complaints of decreased vision during her hospital course. Her initial examination revealed a distance visual acuity of 20/60 in the right eye and counting fingers at 2 feet in the left eye. The fundus examination revealed multiple cotton wool spots and multiple intraretinal hemorrhages in the posterior pole, both more significant in the left fundus than in the right fundus (Figs. 1 and 2); no other ocular findings consistent with vasculitic changes were noted such as keratic precipitates, anterior chamber cell, vitreous cell, or vascular sheathing.
Figure 1. Right Eye of Case 2 Demonstrating Cotton Wool Spots and Mild Retinal Hemorrhages (visual Acuity 20/60).
Figure 2. Left Eye of Case 2 Demonstrating Cotton Wool Spots and Hemorrhages (visual Acuity Counting Fingers).
Her weakness and muscle pain improved marginally during her stay, and at discharge the patient was instructed to take prednisolone 30 mg twice daily (2 mg/kg) and to engage in daily outpatient occupational and physical therapy. During the next 2 weeks, however, partly because her muscle enzymes had stabilized at still elevated values (creatine phosphokinase at 1,373 units/L and aldolase to 18.6 units/L) and mainly due to the severity of her vasculitic disease including her retinopathy, the rheumatology team decided to initiate steroid-sparing treatment with pulse intravenous cyclophosphamide 1,000 mg/m2.
As treatment continued, the patient’s visual acuity and retinal findings improved at subsequent ophthalmic examinations, as did her systemic symptoms. After several months, the patient’s visual acuity improved to 20/20 in the right eye and 20/30 in the left eye, and her creatine phosphokinase level had decreased to 100 to 150 units/L. Her steroids were tapered over 9 months and after completing seven monthly pulses of intravenous cyclophosphamide she was transitioned to oral mycophenylate mofetil for maintenance therapy. No systemic or ocular complications of the treatment were noted.
Juvenile dermatomyositis is a rare and chronic pediatric inflammatory condition with a vascular component involving striated muscles, particularly those proximal of the upper and lower extremities, and skin. This results in progressive muscle weakness and classic skin manifestations, such as Gottron’s papules, heliotrope rash, and periungual capillary changes. The exact cause of this condition is unknown, but both immune and infectious etiologies have been postulated.1 According to published reports, incidence rates range from 1.9 to 4.1 cases per million.2,3 Other organ systems can be involved but these manifestations are less common. Retinopathy associated with dermatomyositis in children was initially described by Bruce in 1938.4 Since then, only a small number of juvenile case reports have been published.5–7
One chart review, conducted at the Hospital for Sick Children in Toronto, showed that more than 50% of patients with juvenile dermatomyositis referred for ophthalmologic consultation had abnormal eye examinations, mainly taking the form of eyelid lesions.8 Only 2 of 82 patients had retinal abnormalities. The mechanism of retinal damage in these patients is likely due to vasculitis with endothelial disruption and resultant retinal ischemia. The retinopathy detected is nonspecific and may include cotton wool spots, intraretinal hemorrhages, macular edema, or macular exudates.
Due to the rarity of the disease and the lack of randomized prospective clinical trials, especially with retinal manifestations, it is difficult to investigate the optimal treatment and develop standard protocols. However, because reports from two decades ago showed that patients with juvenile dermatomyositis had better outcomes when treated with corticosteroids, a popular approach has been to start treatment of juvenile dermatomyositis aggressively with high doses at 2 mg/kg/d with a slow taper after clinical and laboratory improvement are demonstrated.9
However, because of their harmful side effects, particularly in children, corticosteroids have more recently been combined with immunomodulatory agents, such as methotrexate, with the intent of controlling disease while minimizing steroid exposure and subsequent side effects. One study has shown that starting patients with methotrexate 10 to 20 mg/m2/week (maximum: 25 mg/week) and prednisone 2 mg/kg/d may be just as effective as prednisone alone and decreases the length of taper and consequently the associated morbidity.10 Methotrexate is now popularly used as an initial steroid-sparing agent among pediatric rheumatologists for the treatment of juvenile dermatomyositis.
IVIG has also been used with varying success in treating patients with juvenile dermatomyositis. In one retrospective chart review of patients with juvenile dermatomyositis who were either unresponsive to corticosteroid treatment or showed unacceptable toxicity, 12 of 18 had clinical improvement with the use of IVIG.11 IVIG is typically given in a total single dose of 2 g/kg.
It should be noted that the severity of the disease process often influences treatment of juvenile dermatomyositis. It is believed that children with more severe vasculitis as evidenced by gastrointestinal or ocular involvement (retinal ischemia) tend to have worse outcomes and may warrant more aggressive therapy, such as with immunosuppressive agents including cyclophosphamide, tacrolimus, hydroxychloroquine, or azathioprine.12,13
Although most cases of retinopathy associated with juvenile dermatomyositis do improve with appropriate treatment, there have been reports of irreversible retinal damage.14 The two case reports described in the current article illustrate that both retinopathy and visual acuity improve with concurrent treatment of the underlying disease process, and also that findings from a dilated examination may influence the treatment of the disease process. As such, we recommend that rheumatologists routinely ask their patients with juvenile dermatomyositis about visual symptoms. In addition, although retinopathy is rare in patients with juvenile dermatomyositis, having an initial ophthalmic examination should be considered in new-onset juvenile dermatomyositis. The rheumatologists involved in the care of our two patients used their eye findings as factors in their decision to escalate the degree of anti-inflammatory therapy. It is yet to be determined whether ophthalmic changes in juvenile dermatomyositis are a predictor of poor outcome, but in these two cases it was thought to be.