Periorbital Vasculitis Complicating Kawasaki Syndrome in an Infant

ABSTRACT. Periorbital vasculitis is a previously unre- cardiography revealed no aneurysm. Initial labora- ported complication of Kawasaki syndrome (KS). We tory data are summarized in the Table 1. describe an infant with severe KS refractory to initial Treatment3 was initiated on day 7 of illness with management with salicylate and intravenous immuno- rectal salicylate (100 mg/kg/day) and IVIG (2 g/kg) globulin (IVIG). Retreatment with IVIG and high-dose (Polygam, American Red Cross), resulting in partial pulsed steroids was required for persistent fever and inflammatory manifestations. Despite aggressive medi- improvement in KS manifestations (fever, malaise, cal therapy, a large left coronary artery aneurysm devel- rash, edema) and reduction in effusions on chest oped. After apparent complete KS remission, acute peri- film. Recurrent fever (40°C) with irritability orbital vasculitis developed in the left upper and prompted retreatment4 on day 11 with IVIG 1 g/kg, , requiring operative intervention for diagnosis and resulting in a reduction in fever and malaise but in high-dose pulsed steroids for therapy. The significance the development of anaphylaxis (stridor, wheeze, lip of this previously unreported ophthalmic complication swelling) at the terminus of infusion, requiring sub- of KS is reviewed, along with a discussion of the role of cutaneous epinephrine. Echocardiography on day 14 steroids in KS manifestations refractory to IVIG. revealed 4.3 mm of ectasia in the proximal trunk of Pediatrics 1998;101(6). URL: http://www.pediatrics.org/ cgi/content/full/101/6/e9; Kawasaki syndrome; periorbital the left anterior descending (LAD) coronary artery. vasculitis. Rectal salicylate was discontinued after 5 days, when resumption of adequate oral intake allowed high dose oral salicylate (100 mg/kg/day) from day 12 to ABBREVIATIONS. KS, Kawasaki syndrome; IVIG, intravenous day 17. immunoglobulin; CSF, cerebrospinal fluid; LAD, left anterior de- scending; ESR, erythrocyte sedimentation rate; CRP, C-reactive Recurrent fever to 39°C on day 15, with persistent protein. anemia (hemoglobin 5.9 g/dL) and evidence of on- going inflammation (erythrocyte sedimentation rate [ESR] Ͼ 150 mm/hour; C-reactive protein [CRP] ϭ awasaki syndrome (KS) is a systemic vasculi- 14 mg/dL), led to high-dose pulsed steroid therapy5 tis of uncertain etiology.1 Manifestations in for KS refractory to IVIG. The infant received 30 infants, particularly males, can be atypical K 2 mg/kg of methylprednisolone as a single dose over a and unusually severe. We report an infant with KS 4-hour period on day 17, with no complications. and a large coronary aneurysm who responded to Resolution of fever and systemic symptoms was aggressive initial management including intrave- nous immunoglobulin (IVIG) and corticosteroids but prompt and lasting. who subsequently developed periorbital vasculitis, a Echocardiography on day 18 demonstrated a sin- complication previously unreported in KS. gle 6.3-mm aneurysm in the proximal LAD, larger and more fusiform than on study 4 days previously. No myocarditis or effusion was seen. The electrocar- CASE PRESENTATION diogram was normal. The platelet count peaked at In September 1996, a previously healthy breastfed 750 000/mm.3 Despite enlargement of the coronary 8-month-old white boy was diagnosed with KS, aneurysm, the child was playful, ate well, and had a based on the presence of five of six published crite- normal physical examination. Desquamation of 1 ria: 1) fever for 7 days to 40.4°C, refractory to anti- hands and feet was never documented. No hyper- biotics; 2) conjunctival injection, transient and bilat- tension, hematuria, or hepatitis developed. He was eral; 3) edema of all four extremities; 4) adenopathy, discharged on low-dose salicylate (4 mg/kg/day) as with a single posterior cervical node 2 cm in diame- recommended for the subacute phase of KS. ter; and 5) truncal rash, erythematous, macular, and The child remained in clinical remission, gained pleomorphic. Manifestations were severe and also weight, and began to walk at age 9 months. Hemo- included anorexia and irritability despite oral acet- globin increased to 10 g/dL. Total protein, albumin, aminophen, hydrocele formation, ascites, bilateral ESR, and CRP normalized within 2 weeks after ste- pleural effusions, and extreme hypoproteinemia. The roid therapy. Follow-up echocardiography over a sixth criterion for KS diagnosis, enanthem, was not 3-week period demonstrated progressive reduction observed. All bacterial and viral blood, urine, and in aneurysm size from 6.3 to 5.8 mm. He remained on cerebrospinal fluid culture results were negative, as salicylate (4 mg/kg/day). were serologies for several infectious agents. Echo- On day 35 after onset of illness, and 18 days after pulsed IV steroids and apparent KS remission, the infant developed sudden progressive erythema and Received for publication Oct 20, 1998; accepted Feb 13, 1998. distension of the left upper eyelid (Fig 1). No trauma, Reprint requests to (M.W.F.) Department of Family Medicine, Medical College of Georgia, Augusta, GA 30912. fever, exanthem, pain, or irritability was noted, and PEDIATRICS (ISSN 0031 4005). Copyright © 1998 by the American Acad- the child remained playful. General physical exami- emy of Pediatrics. nation was otherwise normal. Ophthalmic examina- http://www.pediatrics.org/cgi/content/full/101/6/Downloaded from www.aappublications.org/newse9 by guestPEDIATRICS on September Vol.26, 2021 101 No. 6 June 1998 1of3 TABLE 1. Initial Laboratory Values and Ancillary Studies appeared edematous and pale on gross inspection. WBC/mm3 7600 The orbital fat appeared slightly edematous but oth- Differential (bands; PMNs; 34; 23; 43 erwise normal, as did the lacrimal gland. The supe- lymphs) (%) rior rectus muscle was inspected via a conjunctival Peripheral smear Toxic granulations; Dohle bodies peritomy and appeared somewhat pale with attenu- Hemoglobin (g/dL) 9.0 ation of the anterior ciliary vessels. Biopsy specimens Platelet count/mm3 345 000 (Fig 2) of the orbicularis muscle showed areas of ESR (mm/hour) 70 panarteritis with leukocytoclasia and a single focus CRP (mg/dL) 12 (normal, Ͻ1) Total protein (g/dL) 4.9 of myositis. Orbital fat showed no significant pathol- Albumin (g/dL) 2.1 ogy, and the temporalis muscle showed only mild Antineutrophil cytoplasmic 1ϩ (by IFA) edema and fibrosis. Special stain studies for bacteria, antibody CSF protein (mg/dL) 36 mycobacteria, and fungi were negative, as were cul- CSF cell count/differential 6/100% lymphs ture results of biopsy specimens. Granulomatosis Electrocardiogram Normal was not noted. The histopathologic findings were Echocardiogram Normal consistent with small- and large-vessel vasculitis ac- companying KS. After discussion with local consultants in ophthal- mology, rheumatology, and infectious disease, and with two nationally recognized KS investigators, the child was treated with pulsed intravenous methyl- prednisolone (30 mg/kg) for 3 days, with dramatic improvement. The left upper eyelid edema de- creased rapidly, and ocular motility steadily im- proved. Ultrasonography and computed tomogra- phy imaging of the chest and abdomen revealed no evidence of vasculitic involvement of the aortic arch, subclavian, pulmonary, renal, or mesenteric arteries. Antinuclear antibodies, antineutrophil cytoplasmic antibodies, and complement were normal. The pa- tient was discharged after 1 week on a slowly taper- ing regimen of oral steroids and long-term aspirin (4 Fig 1. Distended, erythematous left upper eyelid when the pa- mg/kg/day). ESR and CRP normalized within 1 tient was age 9 months. week. On serial follow-up evaluations over a 12- month period, visual acuity was normal bilaterally, tion revealed marked edema of the left upper eyelid, and ocular motility was full without any evidence of with 2 mm of downward displacement of the . . The eyelid incision was well healed and Injection of the left bulbar was more levator muscle function was normal, without . prominent laterally than medially. Ocular motility At age 20 months, and off steroid therapy for 4 was impaired, with a severe deficit of upward gaze months, the child was meeting all growth and devel- in the left eye only. The were equal in size and opment milestones and had a normal physical exam- normally reactive. No afferent pupillary defect was ination. Serial echocardiography over 12 months detected. Visual fixation appeared to be intact bilat- documented progressive normalization of the prox- erally. Dilated ophthalmoscopic examination imal LAD lesion and no new aneurysm formation. showed a normal , , and retinal vessels. Computed tomography revealed an inflam- matory reaction or neoplastic infiltration involving the soft tissues of the left upper eyelid, anterior tem- poral fossa, and superior orbit; the sinuses were nor- mal. White blood cell count was 11 900/mm3 with 19 bands, 24 PMNs, and 39 lymphocytes; hemoglobin was 8.3 g/dL. ESR and CRP were again elevated at 114 mm/hour and 6.2 mg/dL, respectively. Echocar- diography revealed no new or enlarging coronary aneurysms. Diagnostic considerations included or- bital/periorbital , rhabdomyosarcoma, lym- phoma or leukemic infiltrate, and atypical vasculitis. Because of the atypical, progressive nature of the eyelid distension and ophthalmoplegia, and the lack of significant improvement after 24 hours of intrave- nous cefotaxime, surgical exploration and diagnostic biopsy were performed. Incision in the upper eyelid Fig 2. Biopsy of left orbicularis; acute panarteritis (400ϫ magni- crease laterally exposed orbicularis muscle, which fication).

2of3 PERIORBITAL VASCULITISDownloaded from IN www.aappublications.org/news KAWASAKI SYNDROME by guest on September 26, 2021 DISCUSSION nisolone may have a valuable role in managing se- Review of the literature revealed reports of orbital lected vasculitic complications of KS in infants. vasculitis complicating Wegener’s granulomatosis6 and Churg-Strauss vasculitis,7 but not KS. Our case ACKNOWLEDGMENTS did not meet diagnostic or pathologic criteria for We are grateful to Dr Rita S. Jerath, Pediatric Rheumatology; Dr Kenneth A. Murdison, Pediatric Cardiology; and Dr Christopher either of the first two syndromes, which are exceed- B. White, Pediatric Infectious Disease, for helpful insights into the ingly rare in infancy. Our patient did, however, ful- manuscript. fill diagnostic criteria for KS during the initial febrile phase of illness and had histologic evidence compat- Michael W. Felz, MD* ible with KS on subsequent orbital biopsy. Nonoph- Arif Patni, DO* Steven E. Brooks, MD‡§ thalmic focal vasculitis associated with KS has been Rachel A. Tesser, BS§ reported involving subclavian, renal, iliac, mesen- Departments of *Family Medicine, ‡Pediatrics, and 8 teric, and digital arteries. In contrast, the most com- § mon ophthalmologic manifestations of KS are bilat- Medical College of Georgia eral conjunctival injection and nongranulomatous Augusta, GA 30912 iridocyclitis.9 Uveitis10 and with tran- sient vitreous opacities also have been reported.11 REFERENCES Even less common manifestations are dacryocysti- 1. Morens DM, Melish ME. . In: Feigin RD, Cherry JD, tis,12 conjunctival scarring,13 and retinal artery occlu- eds. Textbook of Pediatric Infectious Disease. Philadelphia, PA: Saunders; 14 1992:2123–2139 sion secondary to ophthalmic artery vasculitis. To 2. Levy M, Koren G. Atypical Kawasaki disease: analysis of clinical pre- our knowledge, extraocular muscle palsy and peri- sentation and diagnostic clues. Pediatr Infect Dis J. 1990;9:122–126 orbital vasculitis, as observed in our patient, have not 3. Newburger JW, Takahashi M, Beiser AS, et al. A single infusion of been reported in KS. Not uncommonly, KS patients intravenous gamma globulin compared to four daily doses in the treat- achieve temporary remission of all inflammatory ment of acute Kawasaki syndrome. N Engl J Med. 1991;324:1633–1639 4. Sundel RP, Burns JC, Baker A, Beiser AS, Newburger JW. Gamma manifestations, only to experience rebound symp- globulin retreatment in Kawasaki disease. J Pediatr. 1993;123:657–659 tomatology such as fever and rash several weeks 5. Wright DA, Newburger JW, Baker A, Sundel RP. Treatment of immune after resolution of initial illness. Such patients are globulin-resistant Kawasaki disease with pulsed doses of corticoste- known to be at increased risk for coronary artery roids. J Pediatr. 1996;128:146–149 6. Perry SR, Rootman J, White VA. The clinical and pathological constel- disease. Our patient is distinctive in that clinical re- lation of Wegener’s granulomatosis of the orbit. Ophthalmology. 1997; bound occurred but in an unusual site (the eyelid 104:683–694 and orbit), without fever or new aneurysm forma- 7. Khan NA, Shenoy PK, McClymont L, Palmer TJ. and tion. Our case, then, adds to the spectrum of atypical facial swelling: a case of limited Churg-Strauss syndrome. J Laryngol manifestations of this multisystem vasculitic syn- Otol. 1996;110:578–582 8. Fujiwara H, Fujiwara T, Kao TC, et al. Pathology of Kawasaki disease in drome. the healed stage: relationships between typical and atypical cases of Although the aggressive use of steroids in KS re- Kawasaki disease. Acta Pathol Jpn. 1986;36:857–867 mains controversial,15 especially in patients with cor- 9. Smith LBH, Newburger JW, Burns JC. Kawasaki syndrome and the eye. onary artery aneurysms, our patient demonstrated Pediatr Infect Dis J. 1989;8:116–118 10. Germain BF, Moroney JD, Guggino GS, Cimino L, Rodriguez C, Bo- dramatic improvement with high-dose pulsed meth- canegra TS. Anterior in Kawasaki disease. J Pediatr. 1980;97: ylprednisolone during two serious clinical episodes, 780–781 one life-threatening and one vision-threatening. No 11. Ohno S, Miyajima T, Higuchi M, et al. Ocular manifestations of Ka- adverse effects were observed in our case. In retro- wasaki’s disease (mucocutaneous lymph node syndrome). Am J Oph- spect, the stormy course of the initial febrile phase of thalmol. 1982;93:713–717 12. Mauriello JA, Stabile C, Wagner RS. Dacrocystitis following Kawasaki’s illness, coupled with refractory KS manifestations disease. Ophthal Plast Reconstr Surg. 1986;2:209–211 and coronary aneurysm development despite timely 13. Ryan EH, Walton DS. Conjunctival scarring in Kawasaki disease: a new and repeated IVIG infusions, may have foreshad- finding? J Pediatr Opthalmol Strabismus. 1983;20:106–108 owed a subsequent relapse of some sort, although 14. Font RL, Mehta RS, Streusand SB, O’Boyle TE, Kretzer FL. Bilateral retinal ischemia in Kawasaki disease. Postmortem findings and electron the eye was certainly an unanticipated site. Until the microscope observations. Ophthalmology. 1983;90:569–577 precise role of steroids in KS is clarified in controlled 15. Shulman ST, Rowley AH. Treatment of Kawasaki disease with cortico- studies, we suggest that high-dose methylpred- steroid. J Pediatr. 1996;129:483–485

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Downloaded from www.aappublications.org/news by guest on September 26, 2021 Periorbital Vasculitis Complicating Kawasaki Syndrome in an Infant Michael W. Felz, Arif Patni, Steven E. Brooks and Rachel A. Tesser Pediatrics 1998;101;e9 DOI: 10.1542/peds.101.6.e9

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Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 1998 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

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