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 Table of Contents  
Year : 2022  |  Volume : 2  |  Issue : 3  |  Page : 772-774

A case of adult-onset asthma and periocular xanthogranuloma treated with systemic steroids

1 Department of Ophthalmology, VMMC and Safdarjung Hospital, New Delhi, India
2 Department of Orthopaedics, VMMC and Safdarjung Hospital, New Delhi, India

Date of Submission28-Dec-2021
Date of Acceptance12-Apr-2022
Date of Web Publication16-Jul-2022

Correspondence Address:
Dr. Sukriti Gupta
Room 430, 4th Floor OPD Building, Safdarjung Hospital, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_3073_21

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Adult orbital xanthogranulomatous disease is a rare disorder which may or may not be associated with a systemic involvement. Herein, we report a 60-year-old male who presented with periocular swelling around the eyes for six years with history of asthma and rhinosinusitis. The diagnosis was confirmed by biopsy which showed multiple foci of lymphoid follicles, foamy histiocytes, and macrophages suggestive of the xanthogranulomatous lesion. The findings correlated with adult-onset asthma and periocular xanthogranuloma. He was treated with systemic steroids along with immunomodulator. We report this case owing to rarity of its occurrence, to discuss its management and to create awareness among ophthalmologists about this rare entity.

Keywords: AAPOX, adult orbital xanthogranuloma, asthma, periorbital swelling, steroids, xanthogranuloma

How to cite this article:
Gajashree S, Mehta A, Duvesh RK, Gupta S, Puri G. A case of adult-onset asthma and periocular xanthogranuloma treated with systemic steroids. Indian J Ophthalmol Case Rep 2022;2:772-4

How to cite this URL:
Gajashree S, Mehta A, Duvesh RK, Gupta S, Puri G. A case of adult-onset asthma and periocular xanthogranuloma treated with systemic steroids. Indian J Ophthalmol Case Rep [serial online] 2022 [cited 2022 Aug 11];2:772-4. Available from: https://www.ijoreports.in/text.asp?2022/2/3/772/351172

Adult orbital xanthogranulomatous disease (AOXGD) is an idiopathic inflammatory disorder defined as localized or systemic proliferation of non-Langerhans cell histiocytes characterized by xanthogranulomatous infiltration of the tissues of periorbit and orbit.[1] It is classified into four clinical subtypes based on their systemic involvement.[2] We report a case of adult-onset asthma and periocular xanthogranuloma (AAPOX) subtype due to its rare occurrence and no standard treatment protocol.

  Case Report Top

A 60-year-old male presented with bilateral periocular swelling for six years which was insidious in onset, gradually progressive and painless, causing cosmetic concern. The patient had bronchial asthma for 10 years and rhinosinusitis for three years. Visual acuity, color vision, contrast were normal in both eyes. Extraocular movements were limited to −1 grade in all gazes in right eye. No proptosis or globe displacement. A firm, brownish-yellow, non-tender, periocular swelling more on superior quadrant of bilateral (RE>LE) orbits was noted [Figure 1]. Corrected intraocular pressure by Goldmann applanation tonometry was 28 mmHg in both eyes. Gonioscopy affirmed open angles and fundus examination showed a cup disc ratio of 0.7:1 with inferior neuroretinal rim thinning in RE and 0.6:1 in LE with healthy NRR. He was diagnosed with primary open angle glaucoma for which he was started on eye drop timolol and brimonidine BD in both eyes. There was no organomegaly or lymphadenopathy. Based on the history and examination, differential diagnosis was Graves' ophthalmopathy, non-specific orbital inflammatory disease, Langerhans histiocytes,  Rosai-Dorfman Disease More Details, lymphomas, and adult-onset xanthogranuloma disease. Blood investigations such as complete blood count, blood sugar, lipid profile, liver function test, kidney function test, serum electrolytes, urine analysis, erythrocyte sedimentation rate, angiotensin converting enzyme, venereal disease research laboratory test, toxoplasmosis, rubella, herpes simplex, HIV, cytomegalovirus (IgM/G negative), and thyroid profile were within normal range. Pulmonary function test and abdominal CT scan was unremarkable. Serum protein electrophoresis, antinuclear antibody, rheumatoid factors, absolute eosinophil count, and IgG levels were normal. CECT orbit revealed bilateral preseptal soft tissue thickening and thickened EOM in right eye [Figure 2]. MRI T2W showed diffuse preseptal soft tissue thickening and heterogenous hyperintensity of EOM (R > L) [Figure 3]. Incisional biopsy specimen of preseptal tissue of upper lid revealed the presence of characteristic foamy histiocytes, multiple foci of lymphoid follicles, and macrophages [Figure 4]a and [Figure 4]b. Hence the diagnosis, AAPOX was confirmed.
Figure 1: Bilateral firm, yellowish, non-tender periocular swelling

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Figure 2: CT orbit revealed bilateral preseptal soft tissue thickening (R>L) in both eyes and thickened extraocular muscle in the right eye

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Figure 3: MRI T2W showing diffuse soft tissue thickening seen anterior to orbital septum and heterogenous hyperintensity of extraocular muscles (R>L)

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Figure 4: (a) H and E sections show groups of foamy histiocytes and macrophages (red arrow shows foamy histiocytes) along with lymphocytic inflammatory infiltrate (20×); (b) H and E section shows presence of lymphoid aggregates[blue arrow] with giant cell (red arrow) (40×)

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Oral prednisolone (1 mg/kg body weight) was started and continued for two months. Since swelling was reduced completely [Figure 5] and extraocular movements improved, steroid was tapered over three months and stopped. He developed recurrence after one month of stoppage of oral steroids, hence methotrexate 10 mg was started weekly. After two months of this therapy, eyelid swelling significantly improved [Figure 6] and no recurrence was found even after three months of follow-up. The patient is under regular follow-up to watch for any immune dysfunction or recurrence.
Figure 5: Improvement after 3 weeks of oral steroids

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Figure 6: Improvement after 2 months of methotrexate therapy

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  Discussion Top

Adult orbital xanthogranulomatous disease (AOXGD) is an infiltrative rare disorder of the orbit and its adnexa. Disease prognostication depends upon the subtype of AOXGD:[3],[4],[5]

  • Adult-onset xanthogranuloma (AOX) is the least common type of AOXGD. It has isolated xanthogranulomatous lesions of orbit without systemic involvement.
  • Adult-onset asthma and periocular xanthogranuloma (AAPOX) is associated with immune dysfunction like lymphoproliferative diseases and asthma.
  • Necrobiotic xanthogranuloma (NBX) is the most common type of AOXGD. It manifests as subcutaneous nodules that tend to ulcerate and fibrose.
  • Erdheim–Chester disease (ECD) is defined as lymphohistiocytic infiltration of orbit along with other internal organs such as heart, lung, retroperitoneum, osteosclerotic lesions of bone, and it has worst prognosis.[4]

All subgroups present with ocular adnexal skin lesions involving preseptal and anterior orbit, whereas ECD presents as diffuse intraconal disease.[6] AOXGD presents like xanthelasmas but it extends into deeper tissues and indurated.

The biopsy of AOXGD lesion showed foamy histocytes, Touton giant cells, plasma cells, lymphocytes, and fibroblasts. Additionally, AAPOX had lymphoid follicle aggregates with B cell containing germinal center.[7] The term AAPOX was first described by Jakobiec et al.[8] as an eyelid and orbital lesion. Only 50 cases of AAPOX have been reported till date.[4],[7],[8] It can infiltrate the lacrimal glands and the extraocular muscles[9] and is also associated with adult-onset asthma, and reactive lymphadenopathy with elevated IgG levels. Although its pathogenesis is not clearly described, atopic etiology has been proposed.[9] Association between AAPOX and IgG4-related disease has been found because of common atopic etiology. IgG4-related disease is an autoimmune disease having raised serum IgG4 levels and plasma cell infiltration which may present as chronic lid swelling, dacryoadenitis, scleritis, and myositis.[10–12] In our case, the patient had periocular features along with asthma and rhinosinusitis, but no lymphadenopathy with normal IgG levels.

Owing to its rarity and unavailability of trials, no standard treatment protocol has been charted. Various modalities of treatment were tried such as oral steroids, intralesional steroids, chemotherapeutic agents, debulking surgery, and radiotherapy.[2] Many studies have reported that low-dose steroid therapy may be required for maintaining disease remission. Many reports have described good results with immunomodulators like low-dose methotrexate, cyclophosphamide, and azathioprine along with tapering of oral steroids. In a study by Sahu et al.,[13] AAPOX patient was treated with oral methylprednisolone 12 mg and weekly methotrexate 10 mg for two months. M.B. Green et al.[3] reported a case of AAPOX treated with intralesional triamcinolone and oral cyclophosphamide but recurrence has been reported later.

On account of its accessibility and minimal expense, we initiated oral prednisolone (1 mg/kg body weight) to our patient. Methotrexate 10 mg weekly was started along with 20 mg prednisolone daily following recurrence on stopping oral steroids. LFT/KFT/CBC were monitored regularly on starting methotrexate. Using oral steroids avoids unnecessary complications of surgery and cytotoxic drugs. Patient was consulted by a pulmonologist to rule out any systemic pathology.

In summary, any patient presenting to an ophthalmologist with preseptal swelling with limitation of movements and placoid skin lesions should be evaluated for orbital xanthogranuloma along with Graves' disease, non-specific orbital inflammation (NSOID), lymphomas, etc.Histopathological, radiological, and systemic examinations along with clinical correlation can help to confirm the diagnosis. Also, many patients having adult orbital xanthogranuloma present with orbital and periocular findings first rather than any underlying systemic abnormality. Hence, the ophthalmologists play an important role in correctly diagnosing the disease and referring the patients to the appropriate specialist like rheumatologist, pulmonologist, cardiologist, etc., for timely systemic investigations.

  Conclusion Top

Adult-onset xanthogranuloma is a rare but serious infiltrative disease of the eyelids associated with significant morbidities; hence, a legitimate assessment is important. In our case, long-term low-dose systemic steroids along with immunomodulators proved to be effective in treating AAPOX. Ophthalmologists to whom patients with periocular swelling present first, timely assessment and reference to the concerned specialist is advised.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Karcioglu ZA, Sharara N, Boles TL, Nasr AM. Orbital xanthogranuloma: Clinical and morphologic features in eight patients. Ophthal Plast Reconstr Surg 2003;19:372-8.  Back to cited text no. 1
Davies MJ, Whitehead K, Quagliotto G, Wood D, Patheja RS, Sullivan TJ. Adult orbital and adnexal xanthogranulomatous disease. Asia-Pac J Ophthalmol Phila Pa 2017;6:435-43.  Back to cited text no. 2
Green MB, Daly MK, Laver NMV, Lefebvre DR. Adult-onset asthma, and periocular xanthogranuloma – A rare infiltrative disease of the orbit and eyelid. Am J Ophthalmol Case Rep 2021;22:101043. doi: 10.1016/j.ajoc. 2021.101043.  Back to cited text no. 3
Guo J, Wang J. Adult orbital xanthogranulomatous disease: Review of the literature. Arch Pathol Lab Med 2009;133:1994-7.  Back to cited text no. 4
Sivak-Callcott JA, Rootman J, Rasmussen SL, Nugent RA, White VA, Paridaens D, et al. Adult xanthogranulomatous disease of the orbit and ocular adnexa: New immunohistochemical findings and clinical review. Br J Ophthalmol 2006;90:602-8.  Back to cited text no. 5
Hoffmann EM, Müller-Forell W, Pitz S, Radner H. Erdheim-Chester disease: A case report. Graefes Arch Clin Exp Ophthalmol 2004;242:803-7.  Back to cited text no. 6
Kerstetter J, Wang J. Adult orbital xanthogranulomatous disease: A review with emphasis on etiology, systemic associations, diagnostic tools, and treatment. Dermatol Clin 2015;33:457-63.  Back to cited text no. 7
Jakobiec FA, Mills MD, Hidayat AA, Dallow RL, Townsend DJ, Brinker EA, et al. Periocular xanthogranulomas associated with severe adult-onset asthma. Trans Am Ophthalmol Soc 1993;91:99-125.  Back to cited text no. 8
Cavallazzi Rodrigo, Hirani Amyn, Vasu Tajender S. Clinical manifestations and treatment of adult-onset asthma and periocular xanthogranuloma. Can Respir J 2009;16:159-62.  Back to cited text no. 9
Okazaki K. Autoimmune pancreatitis and IgG4-related disease: The storiform discovery to treatment. Dig Dis Sci 2019;64:2385-94.  Back to cited text no. 10
Wallace ZS, Deshpande V, Stone JH. Ophthalmic manifestations of IgG4-related disease: Single-center experience and literature review. Semin Arthritis Rheum 2014;43:806-17.  Back to cited text no. 11
Kubota T, Moritani S, Katayama M, Terasaki H. Ocular adnexal IgG4-related lymphoplasmacytic infiltrative disorder. Arch Ophthalmol 2010;128:577-84.  Back to cited text no. 12
Sahu K, Sethy M, Sirka CS, Rout AN. Adult-onset asthma with periocular xanthogranuloma (AAPOX), a variant of periorbital xanthogranulomatous disease: An uncommon entity. Indian Dermatol Online J 2020;11:792-5.  Back to cited text no. 13
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]


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