Unusual involvement of IgG4-related sclerosing disease in lacrimal and submandibular glands and extraocular muscles.

Chronic sclerosing sialadenitis, also known as Kuttner tumor, is a chronic inflammatory disease of the salivary glands that is reported in a few cases in medical literature. Recent reports suggest that certain aspects of sclerosing diseases, including chronic sclerosing sialadenitis or dacryoadenitis, should be classified under immunoglobulin G4 (IgG4)-related sclerosing disease based on immunohistochemical studies. This study reports an unusual case of IgG4-related sclerosing disease appearing simultaneously in the lacrimal glands, submandibular glands, and extraocular muscles. A 56-year-old male presented with complaints of bilateral eyelid swelling and proptosis that began two years ago. Computed tomography confirmed that bilateral submandibular enlargements also existed five years ago in the subject. Orbital computed tomography and magnetic resonance imaging revealed bilateral lacrimal gland enlargement and thickening of extraocular muscles. Typical findings of chronic sclerosing dacryoadenitis were revealed upon pathologic exam of the right lacrimal gland. Immunostaining revealed numerous IgG4-positive plasma cells. Through these clinical features, we make a diagnosis of IgG4-relataed sclerosing disease in the subject.

Unusual Involvement of IgG4-Related Sclerosing Disease in Lacrimal and Submandibular Glands and Extraocular Muscles

Chronic sclerosing sialadenitis, also known as Kuttner tumor, is a chronic inflammatory disease of the salivary glands that is reported in a few cases in medical literature. Recent reports suggest that certain aspects of sclerosing diseases, including chronic sclerosing sialadenitis or dacryoadenitis, should be classified under immunoglobulin G4 (IgG4)-related sclerosing disease based on immunohistochemical studies. This study reports an unusual case of IgG4-related sclerosing disease appearing simultaneously in the lacrimal glands, submandibular glands, and extraocular muscles. A 56-year-old male presented with complaints of bilateral eyelid swelling and proptosis that began two years ago. Computed tomography confirmed that bilateral submandibular enlargements also existed five years ago in the subject. Orbital computed tomography and magnetic resonance imaging revealed bilateral lacrimal gland enlargement and thickening of extraocular muscles. Typical findings of chronic sclerosing dacryoadenitis were revealed upon pathologic exam of the right lacrimal gland. Immunostaining revealed numerous IgG4-positive plasma cells. Through these clinical features, we make a diagnosis of IgG4-relataed sclerosing disease in the subject.

Human eyelid meibomian glands and tarsal muscle are recognized by autoantibodies from patients affected by a new variant of endemic pemphigus foliaceus in El-Bagre, Colombia, South America.

BACKGROUND: Previously, we described a new variant of endemic pemphigus foliaceus (EPF) in Colombia, South America (El Bagre-EPF). OBJECTIVE: Continuing our characterization of this variant of EPF, we now focus on one of our previously reported clinical findings: the presence of ocular lesions. These ocular lesions are seen in patients having extensive skin involvement, as measured by the Lund and Browder scale, which is generally used for patients with skin burns. METHODS: We specifically searched for evidence of autoreactivity to various eyelid structures in these patients and correlated our immunologic data with the clinical findings. We performed indirect immunofluorescence studies using normal-appearing human eyelid skin from routine blepharoplasties as substrate tissue. We tested sera from 12 patients with El Bagre-EPF and ocular lesions, 5 patients with sporadic (nonendemic) pemphigus foliaceus, and 20 healthy control subjects (10 from the El Bagre-EPF endemic area and 10 from nonendemic areas). We used fluorescein isothiocyanate conjugated goat antiserum to human total IgG/IgA/IgM as a secondary antibody. In addition, we used fluorescein isothiocyanate conjugated antibodies to human fibrinogen, albumin, IgG, IgE, C1q, and C3, Texas Red (Rockland Immunochemicals, Inc, Gilbertsville, PA), Alexa Fluor 555, or Alexa Fluor 594 (Invitrogen, Carlsbad, CA). Ki-67 (a cell proliferation marker) was used to determine the cell proliferation rate, and nuclear counterstaining was performed with either 4', 6-diamidino-2-phenylindole or Topro III (Invitrogen, Carlsbad, CA). RESULTS: We observed autoreactivity to multiple eyelid structures, including meibomian glands and tarsal muscle bundles at different levels, and some areas of the epidermis and the dermis close to the isthmus of the eyelids. Tarsal plate autoreactivity was seen in 10 of 12 of the El Bagre-EPF sera and in one control with pemphigus erythematosus. Furthermore, immunoprecipitation using an eyelid sample as a substrate with 1 mmol/L of sodium orthovanodate showed autoreactivity to several antigens, including some of possible lipid origin. LIMITATIONS: The main limitation of this study is the fact that the antigen or antigens remain unknown. CONCLUSION: We identified for the first time to our knowledge autoantibodies to meibomian glands and tarsal muscle in El Bagre-EPF. Our findings suggest that the autoantibodies to the ocular structures cause the clinical and histopathological findings in the ocular lesions in El Bagre-EPF.

Correlating extent of neuromuscular instability with acetylcholine receptor antibodies.

In a retrospective study of 86 patients with myasthenia gravis (MG), we correlated the acetylcholine receptor (AChR) antibody titers with single-fiber EMG studies to explore whether a relationship exists between these parameters. We found that the AChR antibody titers correlated significantly with the mean of the mean consecutive difference of orbicularis oculi (OO, P<0.0001) and extensor digitorum communis (EDC, P<0.0001). The correlation was found to be stronger in OO. The antibody titers also correlated with the percentage of potential pairs with increased jitter in both muscles and, again, the correlation was more significant in OO (P<0.0001) than in EDC (P=0.001). We speculate that this relationship is stronger in OO than in the limb muscles, because the architectural and immunological differences in the motor unit render OO more vulnerable and sensitive to disturbances in neuromuscular transmission.

Priming by muscle inflammation alters the response and vulnerability to axotomy-induced damage of the rat facial motor nucleus.

To ascertain whether signaling due to peripheral inflammation affects motoneuron vulnerability, we examined in adult rats the reaction to axonal injury of facial motoneurons primed by muscle inflammation. In this double-hit paradigm, preconditioning was achieved by injections into the facial muscles of the T cell mitogen phytohemagglutinin, which was found in a previous study ( 11 ) to elicit a retrograde response in motoneurons. Facial nerve transection was used as test lesion. Intramuscular injections of saline prior to axotomy were used as control for lectin pretreatment. In rats pretreated with phytohemagglutinin injection, upregulation of the expression of the antiapoptotic bcl-2 gene, examined with in situ hybridization, was significantly higher in facial motoneurons at 2 days postaxotomy compared with saline-injected control cases. After repeated phytohemagglutinin injections followed by nerve transection, induction in facial motoneurons of nitric oxide synthase, revealed by histochemistry and immunohistochemistry, as well as activation of the surrounding microglia, was enhanced at 14 days postaxotomy with respect to the saline-treated control cases. At the same time point, no significant intergroup difference was detected in the intensity of astrocytic activation. At 1 month postaxotomy, stereological cell counts revealed that motoneuron loss was significantly greater in the cases pretreated with phytohemagglutinin than in the saline-treated cases. The data point out that the response of the facial motor nucleus to axonal damage is altered by previous exposure to peripheral inflammation and that such preconditioning stimulus enhances motoneuron vulnerability to nerve injury.

Serum antibody production to botulinum A toxin.

PURPOSE: Conflicting data have been reported regarding development of serum antibodies to botulinum A toxin. The purpose of this study is to determine conclusively whether antibody production to this toxin occurs in humans, and, if so, to determine its relationship, if any, to length of treatment, total cumulative dose, and clinical response to treatment. METHODS: Sixty-five sera samples from 42 adults treated with botulinum A toxin for essential blepharospasm, hemifacial spasm, or spasmodic torticollis were analyzed via a sphere-linked immunodiagnostic assay for antibody production. Results were plotted against length of treatment, number of injections, cumulative dose, and treatment effect produced. RESULTS: Twenty-four (57%) of the 42 patients produced antibodies in all three diagnostic groups. No significant differences were found between antibody producers and nonproducers with respect to age (P = 0.216), length of treatment (P = 0.586), number of injections (P = 0.619), or total cumulative dose (P = 0.286). Within the antibody-producing group, there was no significant correlation between amount of antibody and length of treatment (P = 0.081), number of injections (P = 0.134), or cumulative dose (P = 0.250). The presence of demonstrable antibodies in serum did not affect the clinical responsiveness to injection. CONCLUSION: Antibody production is present in a majority of patients treated with botulinum A toxin. The sphere-linked immunodiagnostic assay is a reliable and reproducible method for detecting and quantifying these antibodies. When antibody production occurs, it is likely due to variations in individual immune responsiveness and appears to have no direct effect on the patient's clinical response to treatment.