Lacrimal and/or salivary gland enlargement is a common symptom leading to referral for rheumatological evaluation. Besides glandular enlargement in Sjögren's syndrome, sarcoidosis, lymphoma and other diseases, the symptom can also be found in IgG4-related disease. This is an increasingly recognized syndrome of unknown etiology comprising a collection of disorders that share specific clinical, serological and pathological features.

Sjögren's syndrome (SjS), an autoimmune disease characterized by exocrine gland dysfunction leading to dry mouth and dry eye diseases, is typified by progressive leukocyte infiltrations of the salivary and lacrimal glands. Histologically, these leukocyte infiltrations generally establish peri-ductal aggregates, referred to as lymphocytic foci (LF), that occassionally appear as germinal center-like structures. The formation and organization of these LF suggest an important and dynamic role for helper T cells (TH), specifically TH1, TH2 and the recently discovered TH17, in development and onset of clinical SjS, considered a B cell-mediated hypersensitivity type 2 disease. Despite an ever-increasing focus on identifying the underlying etiology of SjS, defining factors that initiate this autoimmune disease remains a mystery. Thus, determining interactions between infiltrating TH cells and exocrine gland tissue (auto-)antigens represents a fertile research endeavor. This review discusses pathological functions of TH cells in SjS, the current status of TH cell receptor gene rearrangements associated with human and mouse models of SjS, and potential future prospects for identifying receptor-autoantigen interactions. This article is protected by copyright. All rights reserved.

PURPOSES:

: To assess the tear osmolarity using the TearLab device after laser in situ keratomileusis (LASIK) and to compare the values with those obtained by traditional tear film tests before and after the procedure.

METHODS::

Thirty eyes of 15 refractive surgery candidates (5 men and 10 women of mean age: 30.55 ± 11.79 years) were examined. Using a special questionnaire (Ocular Surface Disease Index), subjective dry eye complaints were evaluated, and then, the tear osmolarity was measured with the TearLab system (TearLab Corporation) and conventional dry eye tests were carried out. Examinations were performed preoperatively and at 1, 30, and 60 days after the surgery.

RESULTS::

The mean value of tear osmolarity was 303.62 ± 12.29 mOsm/L before the surgery and 303.58 ± 20.14 mOsm/L at 60 days after the treatment (P = 0.69). Mean lid parallel conjunctival folds value was 0.68 ± 0.68 before the procedure and 0.58 ± 0.65 subsequent to surgery (P = 0.25). Meibomian gland dysfunction was not detected. No significant deviation was observed in the values of Schirmer test, corneal staining, tear break-up time, and lid parallel conjunctival folds when compared with postoperatively obtained values during the follow-up period (P > 0.05).

CONCLUSIONS::

During LASIK flap creation, intact corneal innervation is damaged, and the ocular surface lacrimal functional unit can be impaired. In our study, no abnormal dry eye test results were observed before or after the procedure. Based on our results, LASIK treatment is safe for dry eye involving the administration of adequate artificial tears for a minimum of 3 months.

PURPOSE:

To assess the impact of recurrent unilateral herpetic keratitis (HK) on the tear secretion of the unaffected fellow eye.

DESIGN:

Prospective, noninterventional study. PARTICIPANTS AND CONTROLS: Thirty-five patients with a history of recurrent unilateral HK (clinically quiescent for at least 3 months) (HK group) and 35 patients who were age- and sex-matched with no history of corneal disease (control group).

METHODS:

Tear osmolarity, tear instability (tear break-up time [TBUT]), tear reflex (Schirmer's I test), and central corneal sensitivity with the Cochet-Bonnet esthesiometer (Luneau, France) were measured in the HK and control groups.

MAIN OUTCOME MEASURES:

Tear osmolarity, TBUT, Schirmer's I, and central corneal sensitivity were compared between the affected and unaffected eyes of the HK and control groups.

RESULTS:

Tear osmolarity and tear secretion reflex were similar between the affected and unaffected eyes of the HK group. Corneal sensitivity and TBUT were statistically lower in the affected eyes compared with the unaffected eyes in the HK group (P = 0.001 and P<0.001, respectively). The central corneal sensitivity of unaffected eyes in the HK group was not significantly different from that in the control group (P>0.05). The tear stability and tear secretion reflex were decreased and tear osmolarity was increased in the unaffected eyes of the HK group compared with the control group (P<0.05, all cases). The difference between unaffected and control eyes varied according to the type of HK. All 4 tests were modified in patients with neurotrophic keratitis (KN). In the keratouveitis subgroup, only corneal sensitivity was normal, whereas Schirmer's I results were also normal in patients with archipelago keratitis. Tear osmolarity was consistently affected in both eyes of herpetic patients.

CONCLUSIONS:

Tear function is impaired in the unaffected eyes of patients with unilateral recurrent HK, even when the disease is apparently quiescent. The higher severity of results in the unaffected fellow eye of patients with KN in comparison with other herpes subgroups suggests that recurrent HK induces a reduction in the afferent pathways of the tear secretion reflex from the affected eye, leading to tear dysfunction in the unaffected eye. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

To characterize a group of patients with IgG4-related disease (IgG4-RD) in a Russian population and to evaluate the efficiency of rituximab therapy.In 2009 to 2011, at the Research Institute of Rheumatology, Russian Academy of Medical Sciences, 30 patients (16 men and 14 women; mean age 44 years) were diagnosed with IgG4-RD that was confirmed by determination of serum IgG4 levels and immunohistochemical study of biopsy samples stained for IgG4-positive plasma cells. Seven patients received rituximab therapy.It was assumed at baseline that there were different types of neoplasias in 12 (40%), non-Hodgkin's and Hodgkin's lymphomas in 10 (33.3%), Sjögren's syndrome in 5 (16.7%), and Wegener's granulomatosis in 3 (10%). When 2 or more locations were involved, the condition was regarded as multifocal fibrosclerosis (33.3%). Localized forms were revealed in 20 (66.7%) patients. Among them, the largest number of patients was those who had orbital pseudotumor, Mikulicz's disease, or retroperitoneal fibrosclerosis. The most common sites of involvement were orbits (66.7%), salivary glands (70%) and lymph nodes (36.7%). Comparison of serum IgG4 levels in 28 patients with IgG4-RD, 22 patients with Sjögren's disease, salivary and lacrimal gland lymphomas, and 10 healthy controls showed that the concentration of IgG4 was significantly higher in Group 1 (median 2.6 g/I; IQR 1.22-4.65 (p < 0.001). Tissue IgG4/IgG ratio varied from 25 to 50% and averaged 38%. A moiré-like pattern of varying fibrosis was noted in 83% of cases. Analysis of laboratory data revealed elevated C-reactive protein concentrations (46.7% with a mean of 39.5 mg/l; normal values < 5.0 mg/l), increased erythrocyte sedimentation rate (60% with a mean of 37.6 mm/h), hypergammaglobulinemia (30% with a mean of 29.4%; normal range 13-22%), and rheumatoid factor (23.3%). After rituximab therapy, all the patients showed a decrease of IgG4 levels to the normal levels and positive changes evidenced by visualization techniques (computed tomography, magnetic resonance imaging).IgG4-RD is a novel problem in modern medicine, which requires a multidisciplinary approach and further study. Rituximab therapy is a promising treatment.

To observe the CT imaging features of anatomic structure related to endoscopic axilla approach for surgery of the frontal recess and frontal sinus.Thirty patients without a history of frontal sinus disease were undergone 16 line high speed spiral computed tomography. The computed tomographic images were analyzed to measure the related structures.The vertical distance from the front attachment point of the middle turbinate to the skull base was 13.88 +/- 2.59 mm. The horyzontal distance from the top point of the axilla of the middle turbinate to the anterior wall of the frontal sinus outflow tract was 5.77 +/- 12.32 mm, to the anterior wall of the nasal cavity was 13.67 +/- 12.54 mm, to the lamina papyracea or lacrimal sac was 5.89 +/- 1.69 mm.Sixteen line high speed spiral computed tomography is helpful to endoscopic axilla approach for surgery of the frontal recess and frontal sinus.

PURPOSE:

: Immunoglobin G4 (IgG4)-related disease is a systemic condition characterized by lymphoplasmacytic infiltrates that can involve the orbit. The purpose of this study was to identify the various patterns of orbital IgG4-related disease on imaging.

METHODS::

Retrospective review of radiologic examinations including CT, MRI, and positron emission tomography was performed in patients with proven cases of IgG4-related disease.

RESULTS::

A total of 9 patients with orbital IgG4-related disease were identified, including 9 with CT, 4 with MRI, and 4 with 18-fluorodeoxyglucose positron emission tomography. Patterns of involvement included lacrimal gland enlargement, lacrimal sac involvement, extraocular muscle thickening, preseptal involvement, orbital fat involvement, and cranial nerve involvement, many of which occurred simultaneously. Associated demineralization of the orbital wall was evident on CT in 2 cases. On T2-weighted MRI, the lesions appeared as hypointense in 2 cases, heterogeneously hypointense to isointense in 1 case, and hyperintense in 1 case. Diffuse enhancement was present in all 3 cases in which postcontrast T1-weighted sequences were available. The lesions were hypermetabolic on positron emission tomography in 3 of 4 cases. There was definite extraorbital involvement by IgG4-related disease in 3 of the 9 patients and suspected involvement in another 3 of the 9 patients.

CONCLUSIONS::

IgG4-related disease displays a wide variety of imaging manifestations in the orbit. Extraorbital disease is often present and can help suggest the diagnosis.

  Sjögren's syndrome (SS) is an autoimmune disease that affects exocrine glands including salivary and lacrimal glands. It is characterized by lymphocytic infiltration into exocrine glands, leading to dry mouth and eyes. A number of auto-antibodies are detected in patients with SS. However, no SS-specific pathologic auto-antibodies have yet been found in this condition. M3 muscarinic acetylcholine receptor (M3R) plays a crucial role in the secretion of saliva. It is reported that some patients with SS carried inhibitory auto-antibodies against M3R. To clarify the epitopes and function of anti-M3R antibodies in SS, we examined antibodies to the extracellular domains (N terminal region, the first, second, and third extracellular loop) of M3R by ELISA using synthesized peptide antigens encoding these domains in 42 SS and 42 healthy controls (HC). Titers and positivity of anti-M3R antibodies to every extracellular domain of M3R were significantly higher in SS than in HC. Our results indicated the presence of several B cell epitopes on M3R in SS. Moreover, we analyzed the functions of anti-M3R antibodies by Ca(2+)-influx assays using a human salivary gland (HSG) cell line. The functional analysis indicated that the influence of such anti-M3R antibodies on Ca(2+)-influx in HSG cells might differ based on the epitopes to which they bind. Interestingly, both IgG from anti-M3R antibodies to the second extracellular loop positive SS and anti-M3R monoclonal antibodies against the second extracellular loop of M3R, which we generated, suppressed Ca(2+)-influx in the HSG cells induced by cevimeline stimulation. These observations suggested that auto-antibodies against the second extracellular loop of M3R could be involved in salivary dysfunction in patients with SS. These results indicated the presence of several B cell epitopes on M3R in SS and the influence of anti-M3R antibodies on salivary secretion might differ based on these epitopes. Thus, anti-M3R antibodies could be not only potential pathologic auto-antibodies, but also new diagnostic makers and therapeutic targets for SS.

Abstract

Purpose:

Rosai-Dorfman disease is a rare, benign, idiopathic histocytic proliferative disorder that typically presents in young adults with painless cervical lymphadenopathy. Here we report an atypical case of Rosai-Dorfman disease involving orbit tissue and lacrimal gland, unilaterally. Case: A 69-year-old Asian women developed a painless palpable mass with local edema over the left upper eyelid over several months. Computed tomography (CT) showed an orbital mass with homogenous soft tissue density over the left lacrimal gland and superior orbital area. The patient underwent complete excision of the orbital tumor. Observations: The histopathology revealed diffuse and nodular infiltrations of S-100 positive histiocytes, plasma cells and lymphocytes. Emperipolesis (lymphocytophagocytosis) was also noted. These findings were consistent with Rosai-Dorfman disease. Chest CT revealed hilar lymphadenopathy. Three months after excision of the orbital mass, the patient developed lymphadenopathy in the extremities that resolved spontaneously over a few weeks. There were no complications or recurrence without systemic treatment after the complete excision.

Conclusions:

Orbital Rosai-Dorfman disease is a rare disorder, especially in Asia. Though there is no consensus on therapeutic choices, including corticosteroids, chemotherapy, radiation therapy, and surgical excision, the complete surgical excision performed in this case was without complication and had a favorable outcome.

Objectives- The purpose of this study was to assess the relationship between the sonographic characteristics of the submandibular glands and organ involvement at the initial presentation in patients with immunoglobulin G4 (IgG4)-related disease. Methods- We conducted a retrospective study that included 15 patients who had bilateral swollen submandibular glands and elevated serum IgG4 levels between January 2005 and December 2010. Results- In all 15 patients, sonography revealed the involvement of both sides of the submandibular glands. The sonographic appearance of each gland was classified into two types: localized tumor-forming and diffuse focal types. On the basis of this typing, all 15 patients were classified into two groups: a group with the localized tumor-forming type observed on one or both sides of the glands (n = 10) and a group with the diffuse focal type present on both sides (n = 5). All 10 patients in the former group had lesions in local exocrine organs, such as the lacrimal and parotid glands, with regional lymphadenopathy. In contrast, all 5 patients in the latter group had lesions in abdominal organs, such as autoimmune pancreatitis and sclerosing cholangitis. Conclusions- The sonographic patterns of the submandibular glands in patients with IgG4-related disease can be divided into two types: localized tumor-forming and diffuse focal. The distinctive patient groups defined by the sonographic patterns in both glands were associated with differential organ involvement and thus could be used as indicators of the disease extension and specific organ involvement.