A fatal presentation of dermatomyositis with facial swelling

International Journal of Pediatric Otorhinolaryngology 76 (2012) 745–749

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Case report

A fatal presentation of dermatomyositis with facial swelling Nishant Dwivedi a, Christie Michael b, D. Betty Lew b, Sandra Arnold b, Masanori Igarashi b, Tulio Bertorini c, Jerome W. Thompson d, Linda K. Myers b, Monica L. Brown b,* a

Departments of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, 38163, United States Departments of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, 38163, United States c Departments of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, United States d Departments of Otolaryngology, University of Tennessee Health Science Center, Memphis, TN, 38163, United States b

A R T I C L E I N F O

A B S T R A C T

Article history: Received 12 December 2011 Received in revised form 30 January 2012 Accepted 31 January 2012 Available online 28 February 2012

Juvenile dermatomyositis (JDM) is the most common inflammatory autoimmune myopathy in children. Most common presentations consist of heliotrophic rash and/or gottron’s papules in addition to proximal muscle weakness. A typical presentations have been reported. We present a 13-year-old African American male who presented with a two-week history of bilateral periorbital edema that was unresponsive to glucocorticoids. He had elevated transaminases but no detectable muscle weakness. A muscle biopsy was consistent with juvenile dermatomyositis. This case highlights the need to consider dermatomyositis in cases of facial swelling and the use of aggressive immunosuppressive therapies due to its associated vasculopathies. Published by Elsevier Ireland Ltd.

Keywords: Periorbital Edema Sinusitis Dermatomyositis Juvenile Vasculitis

1. Case report A 13-year-old African American male presented with a twoweek history of bilateral periorbital swelling, decreased appetite and fatigue. Because of a history of both eczema and allergies to pollens, aspirin, and peanuts, he was treated with anti-histamines and topical steroids. When the swelling did not improve, a CT scan of his sinuses was performed that showed inflammation lining the maxillary, ethmoid and sphenoid sinuses. He was treated with azithromycin (Z-Pak) and Omnicef. Although there was a history of subjective fever, there was no history of muscle weakness, oral ulcers, shortness of breath, itching, skin tightening or recent immunizations. He was an active athlete, played football and lifted weights (up to 80 pounds) regularly. When the periorbital swelling did not improve after treatment with antibiotics, he was admitted to the hospital for further evaluation. At the time of admission, he had bilateral periorbital swelling without erythema or rash (Fig. 1, panel I). A dried yellow pus-like discharge was present in the left eye. Although he complained of blurry vision, he was able to open his right eye with difficulty. The only other abnormality was a dry eczematous rash over both anticubital fossae. His muscle strength tested as 5/5 in all four extremities for both proximal and distal muscle groups. * Corresponding author at: 956 Court Ave, Suite G326, Memphis, TN 38163, United States. Tel.: +1 901 448 5774. E-mail address: [email protected] (M.L. Brown). 0165-5876/$ – see front matter . Published by Elsevier Ireland Ltd. doi:10.1016/j.ijporl.2012.01.037

Laboratory values and infectious disease studies are shown in Tables 1 and 2. The abnormalities included a low white blood count (2.6  103/uL), elevated transaminases [aspartate aminotransferase (AST) 292 and alanine aminotransferase (ALT) 85], elevated creatine kinase of 5037 and an elevated aldolase of 28.2. The patient was started on high dose glucocorticoids and was discharged from the hospital. Despite treatment, the patient did not improve. One month later, he developed upper and lower lip edema (Fig. 1, panel II) and an intermittent low grade fever. The periorbital edema persisted and he acquired an erythematous rash covering his chest and upper arms together with diffuse swelling in both upper arms. Muscle weakness in the hip flexors and shoulder abductors was detected for the first time, eight weeks after the initial presentation. An enlarged left supraclavicular lymph node was also noted. A node biopsy and bone marrow evaluation were performed and neither test gave evidence of a malignancy, although the WBC count decreased to 2.1 and the transaminase enzymes increased (AST, 465; ALT, 99). A trial of systemic antifungal medications and acyclovir was begun and a muscle biopsy was performed. 2. Final diagnosis The biopsy of the sternocleidomastoid muscle showed the presence of inflammatory cells along with perifascicular necrosis

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Fig. 1. Panel (I) Periorbital swelling. Periorbital edema at initial presentation; panel (II) Lip swelling. The left and right panels indicate the degree of lip swelling noted one month after initial presentation; panel (III) Muscle biopsy. (a) Foci of severe muscle necrosis with phagocytosis; (b and c) perifascicular necrosis and vacuolization of muscle fibers; (d) non specific esterase stain showing dark staining macrophages invading necrotic fibers and in the interstitial area ( 40); (e) Alkaline phosphatase stain showing increase activity in capillaries and vessels, ( 100); (f) Inmunoperoxidase stain for MHC-1 showing upregulation of MHC-1 in the surface of muscle fibers; (g) Inmunoperoxidase for CD45 showing numerous positive staining lymphocytes ( 100).

suggesting severe active necrotizing myopathy, consistent with juvenile dermatomyositis (JDM) (Fig. 1, panel III). 3. Hospital course Later that evening, the patient developed bloody diarrhea, which led rapidly to metabolic acidosis, hyperkalemia, and

ventricular fibrillation. Despite resuscitative measures and replacement fluids, he succumbed the following day. A final autopsy revealed two large ulcers in the duodenum with erosion into a submucosal blood vessel. A massive amount of blood was found in the peritoneal cavity indicating intestinal perforation as a cause of hemorrhage and death. Examination of the skeletal muscles identified myonecrosis with inflammation consistent with

Table 1 Laboratory values. Normal range Sodium Potassium Chloride CO2 Urea nitrogen Serum glucose Calcium Creatinine Total protein Albumin Total bilirubin Lactate dehydrogenase Alkaline phosphatase Aspartate aminotransferase Alanine aminotransferase

134–143 mmol/L 3.5–5.0 mmol/L 96–109 mmol/L 20–31 mmol/L 7–17 mg/dL 60–115 mg/dL 8.8–10.8 mg/dL 0.20–0.70 mg/dL 6.3–8.2 g/dL 3.5–5.4 g/dL 0.2–1.2 mg/dL 470–750 units/L 178–455 units/L 15–40 units/L 10–55 units/L

At presentation

Eight weeks

Nine weeks

136 4.6 99 28 10 103 9 0.77 8.1 4.4 0.4 1922 147 292 85

124 4.1 92 26 12 96 8.3 0.76 6.4 3.5 0.5 4537 77 791 170

117 4.8 89 25 23 104 7.3 0.76 5.2 2.5 0.5 – 105 1421 193

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Table 1 (Continued ) Normal range

Eight weeks

Nine weeks

6.0 5.1 10,119

3.9 4.8 18,621

Anion gap Uric acid Creatine kinase (CK) CK-MB Aldolase Free T3 Free T4 TSH

2.39–6.79 pg/ml 0.8–2.0 ng/dL 0.5–4.5 milliunits/mL

9.4 5.1 5037 18.7 28.2 2.86 1.56 1390

Hematology Hemoglobin Hematocrit WBC counts Absolute lymphocytes Erythrocyte sedimentation rate C-Reactive Protein

11–16 g/dL 33–48% 5.0–13.0  103/mL 1.45–7.6  103/mL 0–13 mm/h 5.00–9.00 mg/L

14.1 40.1 2.6 0.73 9 13.20

12.8 36.8 1.9 0.77

11.2 33.5 2.7 0.65

32

42.90

1.020 5.0 Neg Neg Neg Neg

1.020 5.5 Neg 1+ Trace 1+

1.020 5.5 Neg 2+ 3+ Neg

Urinalysis Specific gravity pH Glucose Albumin Blood Ketones Lymphocyte panel CD4+ Cells NK+ Cells C45RO+ cells CD4+/CD8+ ratio

5.0–20.0 2.7–6.7 mg/dL 30–150 units/L 0.6–6.3 units/L

At presentation

1.010–1.035 4.6–8.0

410–1800 68–570 200–980 0.7–4.6

2240

236/uL 59/uL 70/uL 0.8

Laboratory values at presentation, 8 and 9 weeks after presentation.

Table 2 Infectious disease labs. Normal range Viral titers Hepatitis B Surface antigen Hepatitis C antibody HIV-1,2 antibody Rapid HIV Herpes Simplex Virus IgM Ab Reflex HSV-1 IgG HSV-2 IgG Parvovirus B19 IgM IgG Epstein-Barr Virus Nuclear (IgG) EBV IgG EBV IgM EBV Ab to Early-D antigen IgG CMV IgM IgG Bacterial titers B. henselae IgG, IgM screen and titer B. quintana IgG, IgM screen and titer

At presentation

Negative Negative Negative

Bacterial cultures Blood Urine Lip Skin Face Lymph node

Nine weeks

Negative

Negative Negative Negative Negative Not detected

Not detected

0.25 0.20

0.1 5.9

<0.90 <0.90 0.00-0.91 0.00–0.91 0.00–0.91 0.00–0.89

6.80 8.98 0.16 1.66

0.00–0.91 0.00–0.91

7.05 5.66 0.12 1.22 0.12 0.13

Negative Negative

Negative Negative

Fungal titers Histoplasma antigen-urine Histoplasma Ab

Parasite Toxocara Ab Trichinella Ab IgG

Eight weeks

Negative <1:8

<1:8

<1.00 <1.0

Negative Negative

Negative Negative

Negative Negative Negative Negative Negative Negative

Negativeb

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Table 2 (Continued ) Normal range

At presentation

Eight weeks

Nine weeks b

Lung Viral cultures Respiratory Oral mucosa Eye Lymph node Stool

Negative

Fungal cultures Face Oral mucosa Lymph node Bone marrow Pleural fluid Pericardial fluid Lung Liver

Negative

Acid fast bacilli Face Oral mucosa Lymph node Bone marrow Pleural Pericardial

Negative

Anaerobe Face Oral mucosa Lymph node Bone marrow Pleural fluid Pericardial fluid Liver Lung

Negative

Negative

Negative Negative Negative Negative

Negative Negative

Negative Negative Negative Negative Negativea Negativea Negativea Negativea

Negative Negative

Negative

Negative Negative

Negative Negative Negativea Negativea

Negative Negative

Negative Negative Negative

Negative

Negativea Negativea Negativea Negativea

Infectious disease labs obtained through hospital course. a Findings at autopsy. b Of the two blood cultures found at autopsy one grew staphylococcus epidermidis on the third day. Lung tissue and pleural fluid grew staphylococcus epidermidis. These findings at autopsy were felt to be incidental.

dermatomyositis. All pre-mortem cultures were negative (Table 2). The post-mortem cultures were similarly unremarkable, although two were positive for coagulase negative staphylococci, and were considered to be contaminants. Examination of multiple other organs did not reveal any evidence of a malignancy. 4. Discussion Our patient first came to medical attention with the onset of periorbital edema. He had normal muscle strength and did not display the typical juvenile dermatomyositis skin rash (Gottron’s papule, heliotrophic rash or Shawl sign). Although childhood dermatomyositis classically presents with insidious progressive muscle weakness, others have reported cases of JDM presenting as periorbital edema [1]. A retrospective analysis performed on the charts of 50 children at Children’s Hospital, Los Angeles, revealed that 62% of the children with JDM actually presented with head and neck symptoms or signs as the first indications of JDM [2]. The most common symptoms were facial rash (46%), lid edema (26%), documented extremity weakness (24%), muscle pain (18%), and trunk and extremity rash (16%). The upper eyelids commonly have a pathognomonic violet color classically referred to as ‘‘violaceous’’ or ‘‘heliotrope.’’ A more diffuse erythematous rash can also occur on the face, trunk, and joint surfaces, accompanied by edema. Our patient eventually developed a more classical erythroderma and diffuse edema on his upper arms consistent with JDM. Because of the facial swelling, infectious etiologies were considered first. His fever, high respiratory rate, and presence of

a pus-like discharge from the left eye raised the possibility of sinusitis, resulting in treatment with antibiotics and systemic antifungal medications. Cultures of the pus and blood, however, remained negative. The elevated AST, ALT, and LDH were similar to those seen in infections with the parasite Trichinella. Trichinellosis, although low in prevalence in the United States, is caused by a roundworm infection, initiated by ingesting raw or undercooked meats. The larvae can lodge intracellularly in striated muscle cells, causing an intensified local inflammation with associated bilateral periorbital edema and eosinophilia. The muscle biopsy (Fig. 1, panel III) effectively ruled out this diagnosis. The acyclovir was administered because urticaria and periorbital edema can be prodromal presenting signs of an acute hepatitis B infection [3] or herpes simplex virus. Moreover, infectious agents, including viruses such as Coxsackie virus, have been suggested as possible triggers of dermatomyositis [4]. Abnormalities of the thyroid gland were other strong considerations. His high pulse and respiratory rates were consistent with the hyperthyroidism of Graves disease. However the absence of exophthalmos, chemosis or double vision made this diagnosis less likely. Similarly elevated muscle enzymes and periorbital edema without fever can be seen in hypothyroidism. However, both of these diagnoses were ruled out by normal levels of T3, T4 and TSH. People with hereditary angioedema (HAE) can also develop rapid swelling of the hands, feet, limbs, face, intestinal tract, larynx, or trachea. HAE is caused by low levels or improper function of the protein C1 esterase inhibitor. In our case, laboratory testing indicated that the C1 esterase inhibitor level, function and complement levels were normal. The negative ANA (antinuclear

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antibody), anti-Smith, anti-RNP (ribonucleoprotein) and anti-SSA/ SSB tests made systemic lupus erythematosus unlikely as well. Juvenile dermatomyositis is the most common of all inflammatory autoimmune myopathies in children, with an estimated incidence of 2–3 cases/million children/year in the United States [4]. The annual incidence rates by race are about 3.4 in Caucasians, 2.7 in Hispanics and 3 in African-American children [4], and it is found twice as commonly in females than in males [5]. In typical cases patients with dermatomyositis seek medical attention when they develop a characteristic rash or muscle weakness. Muscle weakness is more commonly manifested when the child has difficulty performing routine activities of daily living, such as getting dressed, combing hair, or climbing stairs [6]. The diagnosis of JDM is based on the 1975 criteria of Bohan and Peter [7,8] which outline five components: cutaneous manifestations (heliotrope, Gottron’s papules), symmetrical proximal muscle weakness, muscular enzyme abnormalities, abnormal findings on an electromyogram, and evidence by muscle biopsy of muscle necrosis, perifascicular atrophy, or infiltration of inflammatory cells. The presence of cutaneous manifestations is indispensible, and four additional criteria are usually required to make the diagnosis of JDM: definitive (3 out of 4), probable (2 out of 4) and possible (1 out of 4). Some of the immune laboratory results were abnormal (Table 1). The patient had a low absolute lymphocyte count (690/uL) together with low CD4+ cells, NK cells and C45RO+ cells. On the other hand, the CD3+, CD45RA+, CD19+, CD8+ cells and CD4+/CD8+ ratios were all normal (Table 1). A relatively low ratio of circulating CD45RO+:CD45RA+ has been reportedly attributed to local perivascular accumulation of CD45RO+-activated cells in dermatomyositis [9]. The normal CD8+ makes viral and malignancy etiologies less likely. Most JDM is relapsing, and effective treatment can lead to a long-term remission that is drug-free. With rehabilitation, the child often returns to normal life and activities. However, a subset of JDM patients can develop a serious life-threatening vasculopathy [10]. In these patients, major abnormalities can be found in the walls of the blood vessels, specifically in the endothelial cells of capillaries, arterioles, and veins. Endothelial cells are noted to be in various stages of degeneration and regeneration and the resulting angiopathy causes multiple thrombus formation [10]. Small vessel involvement is often difficult to detect, and extensive involvement of the gastrointestinal tract is frequently fatal. Although rare, the most common cause of death in JDM results from complications of this vasculopathy, including either intestinal hemorrhage or pulmonary sepsis due to repeated interstitial injuries [2]. These observations provide strong support for the concept that dermatomyositis of childhood is a unique disease, and that a fundamental lesion can occur in the walls of blood vessels [10].

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5. Conclusion Here we describe a case of juvenile dermatomyositis (JDM) with an unusual presentation consisting of bilateral periorbital edema, increased muscle enzymes, and rapid death within three months of the initial presentation due to intestinal hemorrhage. In one largescale study of JDM it was found that the average evolution time for the disease before consultation is about 8.5 months [6]. This case highlights the need to maintain high vigilance in diagnosing and treating JDM, especially in cases in which the initial presentation is facial swelling. The possibility that associated vasculopathies can occur underlies the need to consider aggressive immunosuppressive therapies as soon as possible. The treatment of JDM includes high-dose glucocorticoids in addition to disease-modifying agents or cytotoxic agents such as methotrexate.

Funding None.

Conflict of interest All authors have no conflict of interest to declare. References [1] M. Taban, J.D. Perry, Juvenile dermatomyositis presenting with periorbital edema, Ophthal. Plast. Reconstr. Surg. 22 (2006) 393–395. [2] J.W. Thompson, Spontaneous perforation of the esophagus as a manifestation of dermatomyositis, Ann. Otol. Rhinol. Laryngol. 93 (1984) 464–467. [3] R. van Aalsburg, A.P. de Pagter, P.J. van Genderen, Urticaria and periorbital edema as prodromal presenting signs of acute hepatitis b infection, J. Travel Med. 18 (2011) 224–225. [4] E.P. Mendez, R. Lipton, R. Ramsey-Goldman, et al., Us incidence of juvenile dermatomyositis, 1995–1998: results from the national institute of arthritis and musculoskeletal and skin diseases registry, Arthritis Rheum. 49 (2003) 300–305. [5] A. Zouagui, S. Abourazzak, M.L. Idrissi, et al., Actuality of juvenile dermatomyositis, Joint Bone Spine 78 (2011) 235–240. [6] L.J. McCann, A.D. Juggins, S.M. Maillard, et al., The juvenile dermatomyositis national registry and repository (uk and ireland) – clinical characteristics of children recruited within the first 5 yr, Rheumatology (Oxford) 45 (2006) 1255–1260. [7] A. Bohan, J.B. Peter, Polymyositis and dermatomyositis (first of two parts), N. Engl. J. Med. 292 (1975) 344–347. [8] A. Bohan, J.B. Peter, Polymyositis and dermatomyositis (second of two parts), N. Engl. J. Med. 292 (1975) 403–407. [9] L.A. Dourmishev, U. Wollina, Dermatomyositis: immunopathologic study of skin lesions, Acta Dermatovenerol. Alp. Panonica Adriat. 15 (2006) 45–51. [10] B.Q. Banker, Dermatomyostis of childhood, ultrastructural alteratious of muscle and intramuscular blood vessels, J. Neuropathol. Exp. Neurol. 34 (1975) 46–75.