Mikulicz's disease. A case report

Mikulicz's disease. A case report

a r c h s o c e s p o f t a l m o l . 2 0 1 4;8 9(8):332–335 ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGÍA www.elsevier.es/oftalmologia Short com...

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a r c h s o c e s p o f t a l m o l . 2 0 1 4;8 9(8):332–335


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Mikulicz’s disease. A case report夽 I. Coloma-González ∗ , L. Ruíz-García, J. Flores-Preciado, E.O. Encampira-Luna, A. Ceriotto, G. Salcedo-Casillas Departamento de Órbita, Párpados y Vías Lagrimales, Hospital Dr. Luis Sánchez Bulnes, Asociación para Evitar la Ceguera IAP, Mexico City, Mexico

a r t i c l e

i n f o

a b s t r a c t

Article history:

Case report: We report the case of a 48 year-old male with bilateral involvement of the salivary

Received 7 February 2013

and lacrimal glands, which was diagnosed as Mikulicz’s disease by incisional biopsy of the

Accepted 11 June 2013

affected lacrimal glands, which was completely resolved after corticosteroid treatment.

Available online 26 September 2014

Discussion: Sclerosing sialadenitis and/or dacryoadenitis are chronic inflammatory diseases


defined by a persistent and symmetrical swelling of the lacrimal and salivary glands together

Mikulicz’s disease

with elevated serum concentration of IgG4 and tissue infiltration by IgG4 (+) plasma cells.

that are currently classified into IgG4 -related diseases. Specifically, Mikulicz’s disease is

IgG4-related disease

˜ © 2013 Sociedad Espanola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Dacryoadenitis Inflammatory orbital disease

Enfermedad de Mikulicz. A propósito de un caso r e s u m e n Palabras clave:

˜ Caso clínico: Se presenta el caso de un paciente de 48 anos con afectación bilateral de las

Enfermedad de Mikulicz

glándulas lacrimales y salivales que fue diagnosticado de enfermedad de Mikulicz mediante

Enfermedad asociada a IgG4

biopsia incisional de las glándulas lacrimales afectadas, presentando resolución completa


del cuadro tras tratamiento corticoideo.

Enfermedad inflamatoria de la

Discusión: La sialadenitis y/o dacrioadenitis esclerosante son enfermedades inflamatorias


crónicas que, en la actualidad, se clasifican dentro de las enfermedades asociadas a IgG4 . En concreto, la enfermedad de Mikulicz se define por agrandamiento persistente, bilateral y simétrico de las glándulas lacrimales y salivales junto a unas concentraciones elevadas de IgG4 sérica e infiltración tisular importante por células plasmáticas IgG4 (+). ˜ © 2013 Sociedad Espanola de Oftalmología. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.

Please cite this article as: Coloma-González I, Ruíz-García L, Flores-Preciado J, Encampira-Luna EO, Ceriotto A, Salcedo-Casillas G. Enfermedad de Mikulicz. A propósito de un caso. Arch Soc Esp Oftalmol. 2014;89:332–335. ∗ Corresponding author. E-mail address: icg [email protected] (I. Coloma-González). ˜ 2173-5794/$ – see front matter © 2013 Sociedad Espanola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

a r c h s o c e s p o f t a l m o l . 2 0 1 4;8 9(8):332–335


Introduction The term Mikulicz disease (MD) refers to a bilateral, symmetrical, painless edema of unknown origin that affects the lacrimal and salivary glands;1 the term Mikulicz syndrome is only used when the cause of these findings (sarcoidosis, tuberculosis or lymphoma) is known.2 It was initially considered a subtype of Sjögren’s syndrome (SS) due to histopathological similarities. However, this idea was later rejected due to the clear clinical differences between the two conditions.1–3 In 2003, Kamisawa et al.4 proposed that the clinicopathological term for IgG4 -related autoimmune disease encompass a number of conditions with hypergammaglobulinemia and elevated serum concentration of IgG4 ; this group of diseases has included Mikulicz’s disease since 2004, thanks to the contribution made by the Yamamoto group.3 MD diagnostic criteria for Sjögren’s syndrome were defined by the Japanese Company in 20085 and include: symmetric and persistent edema for over 3 months in at least 2 pairs of lacrimal, parotid and/or submandibular glands, in addition to elevated serum concentration of IgG4 (≥135 mg/dl) or histopathological findings of lymphocytic infiltration and IgG4 (+) plasma cells (IgG4 /IgG plasma cells >50%) with tissue fibrosis or sclerosis.

Case report We report the case of a 48-year-old male patient referred to our center due to increased volume of both upper eyelids with 3-year progression along with non-painful submandibular tumors for 2 months. The only previous history reported at admission was an episode of abdominal pain of unknown origin in the previous year. Ophthalmological examination revealed 0.4 visual acuity in the right eye and 0.3 in left eye, without alterations in the anterior or posterior ocular pole. Also, bilateral ptosis of mechanical origin is observed, resulting from two firm and well-defined tumors in the upper outer quadrant (Fig. 1), not causing ocular motility impairment. Exophthalmometry was 18 mm in the right eyeball and 14 mm in the left (Fig. 2). No adenopathies were palpated; however, 2 symmetrical submandibular tumors were, with characteristics similar to palpebral and increased volume of the lower lip (Fig. 3). Orbit CT showed symmetrical lacrimal fossa lesions with density similar to that of soft tissue, not affecting adjacent structures (Fig. 4). Given clinical suspicion of MD, serum IgG and IgG4 analyses were requested, which tested positive for IgG (2114.28 mg/dl) and negative for IgG4 (19 mg/dl). We decided to perform an incisional biopsy of both lesions, which confirmed the diagnosis (Fig. 5). Treatment was initiated with oral prednisone, 1 mg/kg/day for 2 months, with descending posology 3 months thereafter. Response to treatment was good, with no recurrence of symptoms following discontinuation (Fig. 6a and b). Likewise, no malignant transformation was detected after 15 months of

Fig. 1 – Clinical images of patient on admission. Tumors are shown in the outer third of both upper eyelids with secondary mechanical ptosis. Detail of these lesions in lateral vision and with manual elevation of eyelids.

follow-up, although demonstrating this would require a new biopsy of the glandular remnants, which we ruled out for the time being, as there were no signs or symptoms warranting it.

Discussion IgG4 -related disease is a recently reported clinical condition characterized by elevated serum levels of IgG4 and tissue infiltration by IgG4 plasma cells (+) linked to fibrosis.1,6 They can affect various organs, with frequent lacrimal involvement presented as Mikulicz disease and chronic sclerosing dacryoadenitis related to IgG4 .7 Orbital involvement events are more common in women and often have persistent and painless palpebral edema

Fig. 2 – Lower perspective of the patient. We observed relative proptosis of right globe compared to the left.


a r c h s o c e s p o f t a l m o l . 2 0 1 4;8 9(8):332–335

Fig. 3 – Clinical image of lower facial third of the patient on admission. We observed an increase in volume of the lower lip and submandibular tumors due to involvement of submandibular and sublingual salivary glands.

Fig. 4 – Comparative tomography images of orbits, axial slices. Arrows to show lesion sites in the lacrimal fossa.

Fig. 5 – Photomicrographs of incisional biopsy. Above left with HE 40×, abundant inflammatory infiltrate is shown, rich in lymphocytes and plasma cells, as well as the formation of lymphoid nodules (*) and fibrosis (§); this becomes more evident with Masson trichrome (bottom left) Images on the right show slices with immunohistochemical markers 100× revealing numerous mature lymphocytes, CD20, CD4 and IgG4 producing plasma cells.

a r c h s o c e s p o f t a l m o l . 2 0 1 4;8 9(8):332–335


Prognosis is unknown regarding the outcome of patients with orbital involvement. Some exhibit spontaneous regression of symptoms, while in 5–10% of cases this lymphocytic hyperplasia acts as a substrate for lymphoma development.7

Conflicts of interest The authors declare that they have no conflicts of interest.

Thanks Dr. Sánchez Fontán, Chairman of the Board of the Association to Prevent Blindness in Mexico I. A.P.-Hospital Dr. Luis Sánchez Bulnes. Thanks for all the opportunities offered to us year after year. Fig. 6 – Clinical picture of patient outcome. Bulking regression of lacrimal and salivary gland augmentation is shown.

involving the lacrimal gland.7 Additionally, these patients typically have no inflammatory or dry eye symptoms,1 which helps us differentiate it from SS. In our case, the patient showed no signs or symptoms of inflammation or lacrimal dysfunction. His facial appearance is also characteristic of Mikulicz with mechanical bilateral ptosis involving lacrimal glands and difficulty of mouth closure due to enlargement of the salivary glands. In these cases it is important to conduct a comprehensive examination and rigorous questioning since this is a systemic condition that may affect other organs in a synchronous or metachronous manner. In our case, abdominal pain pathology included in medical history could also point to some IgG4 -related symptoms, which were not diagnosed. A series of general and specific criteria of the affected organ is needed for final diagnosis. These include specific laboratory and/or immunohistochemistry tests to differentiate them from other conditions such as idiopathic orbital inflammation, lymphoma or SS.5–8


1. Yamamoto M, Takahashi H, Sugai S, Imai K. Clinical and pathological characteristics of Mikulicz’s disease. Autoimmun Rev. 2005;4:195–200. 2. Schaffer AJ, Jacobsen AW. Mikulicz’s syndrome: a report of ten cases. Am J Dis Child. 1927;34:327–46. 3. Yamamoto M, Takahashi H, Shinomura Y. Clinical practice in immunoglobulin G4-related disease. Isr Med Assoc J. 2012;14:640–1. 4. Kamisawa T, Funata N, Hayashi Y, Eishi Y, Koike M, Tsuruta K, et al. A new clinicopathological entity of IgG4-related autoimmune disease. J Gatroenterol. 2003;38:982–4. 5. Masaki Y, Sugai S, Umehara H. IgG4-related diseases including Mikulicz’s disease and sclerosing pancreatitis: diagnostic insights. J Rheumatol. 2010;37:1380–5. 6. Takahashi H, Yamamoto M, Suzuki C. The birthday of a new syndrome: IgG4-related diseases constitute a clinical entity. Autoinmunity Reviews. 2010;9:591–4. 7. Kubota T, Moritani S. Orbital IgG4-related disease: clinical features and diagnosis. ISRN Rheumatol. 2012:412896. 8. Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012;22:21–30.