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Coronavirus disease 2019 (COVID-19) infection has been linked to numerous autoimmune manifestations. Neither the mechanism nor the etiology of this association has been fully explored or elucidated. Prior studies have detected myositis in patients with proven COVID-19 infection, suggesting a relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the development of myositis. Studies have reported elevated levels of autoimmune antibodies, including myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs), in patients with COVID-19 infection, however the prevalence is not well documented. Our objective was to assess the prevalence of MSAs and MAAs in COVID-19 patients compared with unaffected subjects. Serum samples from 74 unvaccinated, polymerase chain reaction (PCR)-positive COVID-19 infected patients were compared with serum samples from 41 healthy, unaffected individuals. All serum samples were tested for MSA and MAA reactivity. Within the COVID-19-positive group, six (8.1%) patients exhibited MSA/MAA positivity, compared with only one (2.4%) individual from the control group. Although a higher prevalence of MSA/MAA positivity was observed within the COVID-19 infected group, the difference did not reach statistical significance (p=0.223). The autoantibodies detected in this study have a unique association with dermatomyositis and other inflammatory myopathies, and may play a role in COVID-19-associated myopathy. This article was previously presented as an abstract at Jacobs School of Medicine and Biomedical Sciences Research Day on June 3rd, 2022.

Following a similar report on multiple myeloma, Ghione and colleagues report the expected observation that patients with non-Hodgkin lymphoma (NHL) receiving anti-B cell therapies have markedly reduced antibody responses to COVID-19 immunization. Although there is no information regarding T-cell immunity, this suggests that while vaccination is certainly still recommended for this population, patients should be strongly encouraged to maintain social distancing precautions and should be revaccinated after an appropriate interval from the end of their antilymphoma therapy.

Primary Sjögren’s syndrome (pSS) is an autoimmune disease with autoantibodies overproduction, including rheumatoid factors (RF). RF-IgA, IgG immunoglobulin classes are suggested as potential biomarkers of pSS. We studied 76 patients with pSS (ACR/Eular 2017); laboratory tests included ESR, C-reactive protein, concentrations of gamma globulins, RF, Anti-SS-A/Ro, and anti-SS-B/La. Eye dryness and keratoconjunctivitis sicca were confirmed with Schirmer’s test, the ocular staining score (OSS) using lissamine green, fluorescein staining and biopsy of minor salivary gland with the histopathological evaluation. Differences between groups were analyzed with U Mann–Whitney test. Correlations between quantitative variables were assessed with the Spearman correlation coefficient.. The best diagnostic values of immunoglobulin concentration for discriminating pSS patients and healthy individuals are for RF-IgA. With cut-off of 21.5 EU/mL, the sensitivity is 72% and specificity is 100%. Very high specificity (100%) is also obtained for RF-IgM concentration of 74.1 EU/mL. Sensitivity is, however, smaller than that for RF-IgA and amounted to 61%. The RF-IgG is the poorest indicator of pSS with 51% of sensitivity and 95% of specificity. To summarize RF-IgA strongly associate with anti-SS-A and anti-SS-B autoantibodies. Both RF-IgA and RF-IgM may be used as diagnostic tools for pSS. Conclusions: among the three studied rheumatoid factor subtypes, RF-IgA showed the best diagnostic accuracy for pSS. RF-IgA correlated with anti-SS-A/Ro and anti-SS-B antibodies even more closely than RF-IgM. The assessment of the RF-IgA serum concentration may be helpful in the process of establishing pSS diagnosis.

Background: Patients (pts) with cancer have increased morbidity and mortality associated with the development of SARS-Co-V2 infection. The mRNA vaccines BNT162b2 and mRNA-1273 have robust safety and efficacy with 95-97% prevention of severe COVID-19 disease and development of protective antibody titers in 92 - 100% of healthy individuals. By contrast, some pts with hematological malignancy fail to produce anti-spike antibodies (Ab) despite full courses of vaccination. This is particularly true for pts with non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemia (CLL) who are actively treated with or have received B cell-directed therapies (BCT). We recently demonstrated that NHL pts who received the COVID-19 vaccine within 9 months from BCT demonstrated markedly lower rates of seroconversion (11%) compared to healthy individuals (100%) or a cohort of older (age >65y) residents of a nursing home (91.5%). NHL pts who had received BCT more than 9 months before the vaccine responded more robustly (88%) (Ghione et al, Blood 2021). Here, we update the results of our earlier study and perform an analysis to identify factors that may help predict for adequate response to COVID-19 vaccines. We hypothesized that neutrophil (N) or lymphocyte (L) counts and/or N/L ratio (NLR) at baseline might predict for adequate Ab production in response to COVID-19 vaccines after receipt of BCT. Methods: This was an observational study performed at Roswell Park Comprehensive Cancer Center. Pts with NHL/CLL who had received COVID-19 mRNA vaccine were included, vaccine response was assessed as previously described (Ghione et al, Blood 2021). For NLR calculation, pts with CLL or NHL with blood involvement were excluded. Clinical variables were analyzed with the t test and Fisher's exact test; validity and cut-off for the L count was obtained with the ROC analysis using GraphPad9 and SPSS. Results: A total of 142 pts with various types of NHL and CLL receiving standard of care treatments were enrolled. Five pts with prior exposure to COVID-19 infection were excluded from the analysis, reaching a total n=137. Of 83 pts with NHL (n=57) and CLL(n=26) in our cohort who were vaccinated within 9 months of BCT, 14 (17%) seroconverted. Baseline N count (p= 0.5), sex (p= 0.2), age (p= 0.8), number of prior lines of treatment (p= 0.4), type of disease (p= 0.7), time from end of BCT to vaccine (p= 0.7) and type of vaccine (p= 0.08), did not affect the rate of seroconversion. For analysis of N and L counts, 37/137 pts with CLL/NHL involving peripheral blood were excluded. Among the remaining 100 pts, 76 had received/were receiving BCT and 24 were either on observation or were on a treatment not including BCT. Only 26/76 (34%) pts on treatment/previously treated with BCT mounted IgG Ab response, while 22/24 (91.6%) patients who were not on BCT mounted the IgG Ab response (p= 0.007). In these NHL pts (N=100), higher L counts and higher NLR were associated with an increased IgG response to the vaccine (p= 0.019). For pts on BCT (N=76) a higher L count (cut-off of 1455 lymphocytes per cubic millimeter of blood [µL] as noted in the ROC) was associated with a higher rate of COVID-19 vaccine response (p= 0.020, with a sensitivity of 84% and specificity 71.5%). Conclusion: In this study, we confirm that pts with NHL/CLL receiving COVID-19 vaccination while on active treatment or within 9 months of treatment with BCT respond poorly to COVID-19 mRNA vaccination (17% seroconversion). Although a higher lymphocyte count and NLR ratio were associated with improved seroconversion rates, these were not powerful predictors. Further study of specific lymphocyte sub-populations that contribute to effective vaccine induced immunity in the context of BCT is ongoing. These studies will help to define optimal strategies for immunization in patients receiving BCT. Figure 1 Figure 1. Disclosures Torka: TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Griffiths: Takeda Oncology: Consultancy, Honoraria; Alexion Pharmaceuticals: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria; Novartis: Honoraria; Taiho Oncology: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Boston Biomedical: Consultancy; Astex Pharmaceuticals: Honoraria, Research Funding; Genentech: Research Funding; Apellis Pharmaceuticals: Research Funding.

Background: Primary Sjogren’s syndrome (pSS) is an autoimmune disease with the autoantibodies overproduction, including rheumatoid factors (RF). An association of RFs with the disease activity has been already described, with RFs in IgA, IgG immunoglobulin classes suggested as potential biomarkers of immunological/clinical pSS features. Objectives: Examining correlations of RF in IgM, IgA and IgG immunoglobulin classes with other autoantibodies, dry eye tests and histopathological assessment (focus score) of salivary gland inflammation. Methods: We studied 76 patients, mean age 53 (SD=13); (67Female/9Male) with pSS diagnosis (criteria ACR/Eular 2017); mean disease duration from diagnosis 2,24 year. Laboratory tests performed: ESR, C-reactive protein(CRP), concentrations of gamma globulins (g/dl), RF serum concentration assessed using ImmuLisa Enhanced™ RF IgA, IgG, IgM Antibody ELISA IMMCO Diagnostics, Inc. As positive result of the RF-IgA and RF-IgG concentration > 25 EU/mL was considered, as positive RF-IgM > 12,5 EU/mL; a highly positive result set as > 100 EU/mL. Anti-Ro/SSA, and anti-La/SSB antibodies were detected by semiquantitative dot blot method. The eye dryness and keratoconjunctivitis sicca were confirmed with Schirmer’s test (score of less than 5 mm/5’) and the ocular staining score (OSS) using lissamine green and fluorescein staining and biopsy of minor salivary gland with the histopathological evaluation (focus score-FS). The study was approved by the proper ethics committee. Differences between groups were analyzed with U Mann-Whitney test (continuous variables). Correlations between quantative variables were assessed with the Spearman correlation coefficient. Statistical significance was set at p Results: The detection of RF in examined sera: RF- IgA: positive(+) 66% (n=50), negative (-) 34%(n=26); highly positive (++) 51%(n=39); RF-IgG: + 55% (n=42), - 45%(n=34), ++ 9% (n=7); RF-IgM: + 88% (n=67), - 12%(n=9), ++ 55% (n=42). In comparison of patients’ groups: i/RF-IgA (+) vs. RF-IgA(-) : no difference in term of FS, OSS and Schirmer’s test; in RF-IgA(+) group significantly higher anti SS-A antibodies (p=0,002); a significant difference in anti SS-A antibodies level (p=0.028) RF-IgA(++) and lower positive group (less than 100EU/mL); ii/RF-IgM(+) vs. RF-IgM(-): RF-IgM (+) significantly higher anti -SS-A antibodies (p=0.007); iii/RF-IgG (+) vs. RF-IgG(-): RF-IgG(+): RF-IgG(+) significantly higher anti SS-B antibodies (p=0.015). Positive correlation was found between: RF-IgA(+) and RF- IgG(+) (rho=0.647) and RF- IgM(+) (rho= 0.669); RF-IgG(+) and RF-IgM(-) (rho=0.429). Surprisingly no correlations found in studied group between concentrations of RF- IgA, IgG and IgM and WBC, C4, C3 complement component, FS, OSS, and Schirmer’s test. Conclusion: 1. rheumatoid factors in main three classes of gammaglobulins, particularly RF-IgA, strongly associate with anti-SSA and anti-SSB autoantibodies production. 2. RF – IgM and RF- IgA dominate over RF- IgG in pSS. 3. both RF-IgA and RF-IgM may be used as diagnostic tool for pSS. 4. Further research is needed to distinguish activity and role of RF- IgA based upon its presence in serum vs. in saliva. References: [1] Peen E, Mellbye OJ, Haga HJ. IgA rheumatoid factor in primary Sjogren’s syndrome. Scand J Rheumatol. 2009 Jan-Feb;38(1):46-9. [2] Garcia-Carrasco M, Mendoza-Pinto C, Jimenez-Hernandez C, Jimenez-Hernandez M, Nava-Zavala A, Riebeling C. Serologic features of primary Sjogren’s syndrome: clinical and prognostic correlation. Int J Clin Rheumatol. 2012;7(6):651-659. Disclosure of Interests: None declared

Objective Although antinuclear autoantibody (ANA) staining of oral biopsy specimens is indicative of chronic ulcerative stomatitis, it is not known whether this staining is characteristic of other autoimmune diseases. Our study was undertaken to characterize the various in vivo ANA patterns detected in the oral mucosa by direct immunofluorescence to describe the associated hematoxylin and eosin findings, and determine whether patients with these findings had a coexisting systemic connective tissue disease. Study Design This was a retrospective analysis of oral biopsy specimens submitted from 2013 to 2016. Results In vivo ANA staining was present in 72 of the 2019 cases examined. Immunoglobulin G was the most common immunoreactant (71 of 72 cases), and speckled nuclear staining was the most frequent in vivo ANA pattern (52 of 72). In most cases, hematoxylin and eosin staining of biopsy specimens showed mucositis (24 of 34). Detailed clinical information was available for 10 patients, and all of them had an autoimmune disease. Conclusions We found similar prevalence of ANA staining with direct immunofluorescence in oral epithelial biopsy specimens as reported for those of skin. In vivo ANA in the oral epithelium may indicate the presence of an immune-mediated disease. Patients who show ANA deposits in oral mucosal biopsy specimens should be investigated for systemic connective tissue disease as well as for chronic ulcerative stomatitis.

Animal models that recapitulate human disease are crucial for the study of Sjogren's Syndrome (SS). While several SS mouse models exist, there are few primary SS (pSS) models that mimic systemic disease manifestations seen in humans. Similar to pSS patients, NOD.B10Sn-H2b/J (NOD.B10) mice develop exocrine gland disease and anti-nuclear autoantibodies. However, the disease kinetics and spectrum of extra-glandular disease remain poorly characterized in this model. Our objective was to characterize local and systemic SS manifestations in depth in NOD.B10 female mice at early and late disease time points. To this end, sera, exocrine tissue, lung, and kidney were analyzed. NOD.B10 mice have robust lymphocytic infiltration of salivary and lacrimal tissue. In addition, they exhibit significant renal and pulmonary inflammation. We identified numerous autoantibodies, including those directed against salivary proteins. In conclusion, the NOD.B10 model recapitulates both local and systemic pSS disease and represents an excellent model for translational studies.

Indirect immunofluorescence (IIF) using human epithelial cell (HEp-2) substrate is a widely used and the recommended method for screening of antinuclear antibodies (ANA). Dense fine speckled (DFS70) pattern on HEp-2 has been widely reported in various healthy and disease groups. Interpretation of DFS70 pattern can be challenging on a conventional HEp-2 substrate due to its similarity to some of the disease associated patterns. The high prevalence of DFS70 autoantibodies in normal population, lack of association with a particular disease group and a general negative association with systemic and ANA associated autoimmune rheumatic diseases (SARD/AARD) necessitates the confirmation of DFS70 pattern. Results using available commercial assays for confirmation of DFS70 autoantibodies do not always agree with IIF screening results further complicating the lab work flow and ANA algorithms. In this review, we discuss the prevalence of DFS70 antibodies and factors affecting the performance of IIF and DFS70 specific confirmatory assays. Factors that contribute to disagreement between DFS70 suspicion by IIF and confirmatory assays will also be discussed. In addition, we also describe a novel IIF HEp-2 substrate, and its positive impact on DFS70 reporting and ANA screening-confirmation algorithm.

The presence of autoantibodies is one of several hallmarks of Sjogren's Syndrome, the detection of serum autoantibodies has a central role in the diagnosis and classification of Sjogren's syndrome. In this review, we will discuss autoantibodies that are helpful in the diagnosis of Sjogren's syndrome. This includes the traditional autoantibodies for disease classification (ANA, Anti-Ro/SSA, Anti-La/SSB, RF), autoantibodies identified from mouse models (Anti-SP1, Anti- PSP, Anti-CA6, and anti-alpha fodrin) and autoantibodies associated with other autoimmune disease (ACA, AMA, and Anti-CCP). We will also review the methods for the detection of autoantibodies and associated challenges for clinical results reporting. The significance of using an autoantibody panel for the diagnosis of SS will be also be reviewed.

Background: Antibodies to salivary gland protein 1 (SP1), carbonic anhydrase 6 (CA6) and parotid secretory protein (PSP) were discovered in an animal model of Sjogren’s syndrome (SS). Their expression was noted in patients with SS, especially those with lower focus scores on lip biopsies and those with early disease lacking antibodies to Ro and La. Objective: The current studies evaluated these autoantibodies in patients with long-standing SS expressing high levels of anti-Ro antibodies and in patients with Sjogren’s syndrome secondary to systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and mixed connective tissue disease (MCTD). Method: Sera were obtained from patients and evaluated by ELISA for IgG, IgA and IgM antibodies to SP1, CA6 and PSP. Results: IgA anti-CA6 antibodies were noted in 38% of these patients, but anti-SP1, CA6 and PSP IgM or IgG antibodies were identified only in a minority of patients. In patients with secondary SS, antibodies to SP1/CA6/PSP were more sensitive and specific than anti-Ro . Conclusion: While more studies are needed, antibodies to SP1, CA6 and PSP provide valuable markers for the diagnosis of primary and secondary SS, especially early in the course of the disease.

Sjogren's syndrome (SS) has been associated with the expression of anti-Ro and anti-La antibodies. Anti-salivary gland protein 1 (SP1) antibodies have recently been identified in patients with SS. The current work involved a cross sectional study to determine whether anti-SP1 antibodies were identified in particular subgroups of patients with SS. The results of this study revealed that anti-SP1 antibodies were present in the sera of 52% of SS patients while anti-Ro/anti-La was present in 63% of patients. 19% of patients had anti-SP1 without anti-Ro/anti-La. Patients with SS and lymphoma expressed anti-Ro, anti-La and anti-SP1 together. In SS associated with RA, 50% had antibodies anti-SP1 while 40% had anti-Ro/anti-La. In conclusion, anti-SP1 antibodies are commonly seen in both primary and secondary SS and rarely in normal controls. Future studies are needed to determine the roles and timing of expression of anti-SP1 antibodies in Sjogren's syndrome.

Purpose: The purpose of this report is to describe 2 patients with persistent severe dry eyes, positive Schirmer tests for Sjogren's syndrome (SS) but lacking antibodies to either Ro or La. These patients were diagnosed to have SS by detecting antibodies to salivary gland protein 1 (Sp1) and parotid secretory protein (PSP). This report emphasizes the existence of patients with SS who lack antibodies to either Ro or La and may therefore be misdiagnosed. Detection of novel autoantibodies, including antibodies to Sp1 and PSP, are helpful in identifying these patients. Initial presentation may simply be dry eyes. Methods: Two patients who presented to our ophthalmology clinic are described. One of the patients underwent multiple procedures over a period of 10 years for severe xerophthalmia. The other patient had rheumatoid arthritis and xerophthalmia. However, in both patients, chronic xerophthalmia had been considered to be idiopathic because antibodies Ro and La were negative. Further serologic testing revealed antibodies to Sp1 and PSP. Results: Two patients who lacked antibodies to Ro and La but not to Sp1 and PSP were diagnosed as having SS. Conclusion: Patients presenting with unexplained dry eyes may not always show the serology markers in the current criteria for SS, anti-Ro and anti-La. In these cases, investigation for novel, early antibodies to Sp1 and PSP is of importance in the diagnosis of SS.

Primary Sjögren’s syndrome (pSS) is a complex autoimmune disease starting in the salivary and lacrimal glands and continuing to involve the lungs and kidneys with the eventual development of lymphoma. Many studies have emphasized the role of type 1 IFN (IFN-α) and lymphotoxin α (LTα) in the pathogenesis of the disease. The present studies were designed to delineate the role of IFN-α in pSS using an animal model, the IL-14α (IL14αTG) transgenic mouse. IL14αTG mice lacking the type 1 IFNR (IL14αTG.IFNR−/−) had the same submandibular gland and lacrimal gland injury as did the IL14αTG mice, but they lacked the later parotid gland and lung injury. Development of lymphoma was delayed in IL14αTG.IFNR−/− mice. The switch from IgM to IgG autoantibodies as well as the increase in serum IgG2a seen is IL14αTG mice was inhibited in IL14αTG.IFNR−/− mice. Production of LTα was identified in both IL14αTG mice and IL14αTG.IFNR−/− mice at the time that salivary gland injury was occurring. These and previous studies suggest a model for pSS that separates the disease into several stages: 1) initial injury to the submandibular and lacrimal glands via an environmental insult and LTα; 2) amplification of local injury via the production of type 1 IFN; injury to the parotid glands, lungs, and kidneys is seen; 3) progression of systemic inflammation with the eventual development of large B cell lymphoma. Understanding these different stages will help to develop strategies for treatment of patients with pSS based on the status of their disease.

Sjogren's syndrome (SS) is defined by autoantibodies to Ro and La. The current studies identified additional autoantibodies in SS to salivary gland protein 1 (SP-1), carbonic anhydrase 6 (CA6) and parotid secretory protein (PSP). These autoantibodies were present in two animal models for SS and occurred earlier in the course of the disease than antibodies to Ro or La. Patients with SS also produced antibodies to SP-1, CA6 and PSP. These antibodies were found in 45% of patients meeting the criteria for SS who lacked antibodies to Ro or La. Furthermore, in patients with idiopathic xerostomia and xerophthalmia for less than 2 years, 76% had antibodies to SP-1 and/or CA6 while only 31% had antibodies to Ro or La. Antibodies to SP-1, CA6 and PSP may be useful markers for identifying patients with SS at early stages of the disease or those that lack antibodies to either Ro or La.

Sjogren’s syndrome (SS) is a complex heterogeneous autoimmune disease resulting in loss of salivary gland and lacrimal gland function that may include multiple systemic manifestations including lymphoma. Multiple cell types participate in disease pathogenesis. This review discusses evidence for abnormal B cell subpopulations in patients with SS, critical roles of B cells in SS and the status of B cell–directed therapies in the management of patients with SS.

Squamous odontogenic tumor (SOT) is a rare benign epithelial odontogenic neoplasm of the jaws. Both intraosseous and peripheral SOTs have been described in the English language literature. While most intraosseous SOTs occur as solitary lesions, a multicentric variant has also been previously described. Although the radiographic and microscopic features are identical for both solitary and multicentric clinical presentations, there are three significant differences between them. More specifically, multicentric SOT presents at an earlier age (third decade of life), has a slightly higher male to female ratio than the solitary type and has a marked predilection for African-Americans. Here we document the eighth reported case of multicentric SOT, which was diagnosed in a 43-year-old African-American male. In addition, we feature focal sebaceous metaplasia, a heretofore unknown microscopic feature of SOT. Clinical, radiological, and histopathological findings are discussed. The differential diagnosis, biological behavior and management modalities for SOT are also addressed.

Patients with Sjogren's syndrome (SS) have been shown to have abnormal B cell function and increased numbers of marginal zone B cells (MZB and MZB precursors. The current studies utilized the Interleukin 14 alpha transgenic mouse model (IL14aTG) for SS to investigate the roles of marginal zone B cells (MZB) of the innate immune system in the pathophysiology of the disease. Eliminating MZB from IL14aTG mice by B cell specific deletion of RBP-J resulted in complete elimination of all disease manifestations of SS. Mice had normal salivary gland secretions, negative autoantibodies and normal histology of the salivary and lacrimal glands compared to IL14aTG mice at the same time points. In contrast, eliminating B1 cells by deleting btk did not ameliorate the disease. Therefore, MZB are critical for the development of SS.

To compare frequencies of autoreactive antibody responses to endogenous disease-associated antigens in healthy controls (HC), relapsing and progressive MS and to assess their associations with clinical and MRI measures of MS disease progression. Methods The study analyzed 969 serum samples from 315 HC, 411 relapsing remitting MS (RR-MS), 128 secondary progressive MS (SP-MS), 33 primary progressive MS (PP-MS) and 82 patients with other neurological diseases for autoantibodies against two putative MS antigens CSF114(Glc) and KIR4.1a and KIR4.1b and against 24 key endogenous antigens linked to diseases such as vasculitis, systemic sclerosis, rheumatoid arthritis, Sjogren’s syndrome, systemic lupus erythematosus, polymyositis, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease and primary biliary cirrhosis. Associations with disability and MRI measures of lesional injury and neurodegeneration were assessed. Results The frequencies of anti-KIR4.1a and anti-KIR4.1b peptide IgG positivity were 9.8% and 11.4% in HC compared to 4.9% and 7.5% in RR-MS, 8.6% for both peptides in SP-MS and 6.1% for both peptides in PP-MS (p = 0.13 for KIR4.1a and p = 0.34 for KIR4.1b), respectively. Antibodies against CSF114(Glc), KIR4.1a and KIR4.1b peptides were not associated with MS compared to HC, or with MS disease progression. HLA DRB1*15:01 positivity and anti-Epstein Barr virus antibodies, which are MS risk factors, were not associated with these putative MS antibodies. Conclusions Antibody responses to KIR4.1a and KIR4.1b peptides are not increased in MS compared to HC nor associated with MS disease progression. The frequencies of the diverse autoreactive antibodies investigated are similar in MS and HC.

Pityriasis rubra pilaris is a chronic, papulosquamous dermatosis of unknown etiology. Oral mucosal involvement of this condition is rare with only 3 previously reported cases in the English literature. A case of a 68-year-old man with pityriasis rubra pilaris with involvement of tongue and palate is presented. Clinical features, histopathologic features, and management of pityriasis rubra pilaris are discussed. We hereby present an additional case, the fourth worldwide, and review the literature.

Sarcoidosis is a common systemic granulomatous disease affecting multiple organs. Oral involvement is relatively rare and, to our knowledge, there have been only 64 cases reported in the English literature. Most cases of oral sarcoidosis present with mobility of the teeth due to rapid alveolar bone loss. Other oral manifestations include asymptomatic swelling of the involved mucosa, gingivitis and ulcers. Diagnosis of sarcoidosis is by exclusion as no specific test is available. Radiographic, biochemical and histological findings are non-specific, but helpful. All cases of sarcoidosis do not require treatment. Corticosteroids are the treatment of choice in patients requiring treatment. Other drugs such as chloroquine, methotrexate, infliximab and thalidomide are also used in the treatment of sarcoidosis. In most of the oral cases reported, systemic steroids and surgery were the preferred treatment.

Sarcoidosis is a relatively common systemic granulomatous disease of unknown etiology. The skeletal system is affected in up to 39% of patients, but intraosseous sarcoidosis affecting the maxilla and mandible is rare. Only 20 cases have been reported previously in the English literature. This paper presents a case of generalized intraosseous sarcoidosis of the jaw bones that mimicked rapidly progressive periodontitis.A 46-year-old male patient presented with loose teeth for assessment of implants. He had been gradually losing his teeth since 1999. His past medical history was significant, with sarcoidosis diagnosed in 1998. A panoramic radiograph showed a bilateral cotton-wool appearance of the mandible. A soft tissue and bone biopsy was performed and sent for histological examination.Microscopic examination of hematoxylin and eosin-stained sections revealed non-caseating granulomatous inflammation consistent with skeletal sarcoidosis.Intraosseous sarcoidosis of the jaw bones is rare and presents commonly as progressive and rapid alveolar bone loss similar to periodontitis. Therefore, it is important for periodontists to be knowledgeable and able to diagnose this condition, as rapid alveolar bone loss may be the first sign of sarcoidosis.

A definitive diagnosis is crucial for management of any oral mucosal disease. Direct immunofluorescence (DIF) is a valuable diagnostic aid for immune-mediated blistering diseases and systemic connective tissue diseases of the skin and the mucosa. This paper gives an overview of the DIF biopsy technique for oral lesions and provides a background for the clinician to optimize the utilization of DIF biopsy. The key characteristic diagnostic findings of DIF of specific mucosal diseases are also discussed.

Background Sjogren’s syndrome (SS) is a chronic autoimmune disease mainly affecting salivary and lacrimal glands. Current diagnostic criteria for SS utilize anti-Ro and anti-La as serological markers. Animal models for SS have identified novel autoantibodies, anti-salivary gland protein 1 (SP1), anti-carbonic anhydrase 6 (CA6) and parotid secretory protein (PSP). These novel antibodies are seen in the animals at an earlier stage of SS than anti-Ro and anti-La. The current studies were designed to evaluate these novel autoantibodies in the sera of well-characterized patients with dry eyes and dry mouth and lip biopsies from the Sjogren’s International Collaborative Clinical Alliance (SICCA) to determine if they indeed identify SS with less severe disease than patients expressing anti-Ro and anti-La. Methods Sera were obtained from SICCA registry in patients for whom lymphocytic foci per 4 mm2 on the lip biopsies was either 0 (F = 0), 3 (F >3). ELISA assays were utilized to evaluate these sera for anti-Ro, anti-La, anti-SP1, anti-CA6, and anti-PSP. Results In patients with dry eyes and dry mouth but F = 0, increased expression of anti- CA6 was noted compared to the F 3 group (p = .006). Neither anti-PSP nor anti-SP1 reached statistical significance because of the small numbers in the F0 group, although there was a trend for their expression to be higher in the F0 group. On the other hand, the expression of anti-Ro was significantly reduced in the F0 group compared to the F 3 (p = .0003) groups. The reduced expression of anti-La in the F0 group compared to the F 3 groups did not quite reach statistical significance. Conclusions Anti-Ro and anti-La identify patients with SS and more severe disease than anti-SP1, anti-CA6, and anti-PSP. More studies are needed to identify the timing in the course of SS when these different autoantibodies are expressed and/or whether they are expressed in patients with different clinical manifestations.

Sarcoidosis is a multi-system, non-caseating granulomatous disease of unknown aetiology that may affect any organ. The oral involvement of sarcoidosis is rare and usually an initial manifestation of the disease. In this case report the authors present a 25-year-old African-American woman with palatal sarcoidosis treated successfully with intra-lesional corticosteroid injections. The oral manifestationsof sarcoidosis are relatively uncommon and may be the only manifestation of the disease. Suspected cases of oral sarcoidosis should be biopsied and subsequently referred to a physician to rule out systemic involvement.

Background An early and accurate diagnosis of Sjogren9s Syndrome is an important factor in limiting complications of the disease. Achieving this diagnosis has historically proved challenging, requiring a number of diagnostic tests including serology [1]. The utility of the traditional serological markers (SSA/Ro, SSB/La, Antinuclear Antibody, Rheumatoid Factor) have several limitations, including a combined sensitivity and specificity of approximately 40–60%, lack of detectability in approximately 20–30% of cases, lack of detectability early in the disease process, and lack of target-organ specificity [1,2]. Sjo™ is an advanced diagnostic panel for the early detection of Sjogren9s Syndrome. It includes the traditional biomarkers as well as three novel, proprietary biomarkers (SP-1, CA6, PSP) that provide high sensitivity and specificity for Sjogren9s Syndrome, are target-organ specific and appear early in the disease process [3,4]. Objectives To Evaluate the sensitivity and specificity of the advance Sjo panel in comparison to the traditional serological markers. Methods Antibodies to the traditional markers (SSA [Ro], SSB [La], antinuclear antibody [ANA], and rheumatoid factor [RF]) and the novel biomarkers (salivary protein-1 [SP1], carbonic anhydrase-6 [CA6] and parotid secretory protein [PSP]) in patient sera samples were detected using the Sjo panel. To assess sensitivity, sera samples from 267 confirmed SS patients across 3 clinical studies were analyzed with Sjo. To assess specificity, sera samples from 125 age- and sex-matched controls, as well as 64 pediatric controls, were analyzed with Sjo. Results Overall, the cumulative sensitivity of the complete Sjo panel was 91.4% (244/267); sensitivity of SSA/SSB alone was 74.9% (200/267), while sensitivity for the novel biomarkers alone was 49.8% (133/267). The cumulative specificity for the complete Sjo panel was 79.8% (151/189), and the cumulative specificity for the novel biomarkers was 83.5% (158/189). Conclusions An early and accurate diagnosis of SS is an important factor in limiting complications of the disease. The Sjo panel incorporates traditional and novel markers and increases the sensitivity in the diagnosis of SS by over 25% without compromising specificity. Patients who may have SS would benefit from screening with the Sjo panel to facilitate early diagnosis and contribute to better management of dry eye symptoms and other systemic manifestations. References Sjogren Syndrome Foundation. Available at Http://www.sjogrens.org Ramos-Casals M, Brito-Zerόn P, Sisό-Almirall A, Bosch X. Primary Sjogren9s Syndrome. BMJ 2012;344:e3821 doi: 10. 1136/bmj.e382 Shen L, Suresh L, Lindemann M, Xuan J. Kowal P, Malyavantham K. Ambrus JL. Novel autoantibodies in Sjogren9s syndrome. Clin Immunol 2012:145;251–25 Shen, L., Kapsogeorgou, E. K., Yu, M., Suresh, L., Malyavantham, K., Tzioufas, A. G,.Ambrus, J. L., Jr. Evaluation of salivary gland protein 1 antibodies in patients with primary and secondary Sjogren9s syndrome. Clin Immunol 2014: 155; 42–465. Suresh, L., Malyavantham, K., Shen, L., Ambrus, J. L., Jr. Investigation of novel autoantibodies in Sjogren9s syndrome utilizing Sera from the Sjogren9s international collaborative clinical alliance cohort. BMC Ophthalmol 2015, 15;38–42 Disclosure of Interest None declared

Background: Desquamative gingivitis (DG) is a common clinical manifestation of oral autoimmune vesiculobullous diseases (VBDs). Their polymorphous clinical presentations coupled with similar histologic features make diagnosis indistinguishable among the different VBDs. Direct immunofluorescence (IF) studies are valuable gold-standard diagnostic tests that allow for discrimination among the various VBDs that present with DG. There have been no recent detailed analyses done that have used conventional light microscopy and direct IF in diagnosis to document the clinical associations of DG with various autoimmune oral diseases. The aim of this study is to examine retrospectively a large cohort of patients with DG for associated diseases and to determine the utility of direct IF and conventional light microscopy in establishing a definitive diagnosis. Methods: During a 14-month period, our laboratory in Buffalo, New York, received 239 consecutive archival cases of gingival biopsy with a clinical diagnosis of DG. These specimens were submitted to establish or rule out a diagnosis of a direct IF–positive VBD. The demographic, clinical, and microscopic findings were tabulated using established inclusion and diagnostic criteria. Results: Approximately half the number (48.1%) of biopsies received for direct IF studies were submitted by periodontists. Slightly more than half of the patients (53%) previously had biopsies submitted for both hematoxylin and eosin (H& E) and direct IF testing. There was a female predilection for all the diseases studied except for pemphigus and linear immunoglobulin A disease. Oral lichen planus was the most common disease presenting as DG, followed by pemphigoid. The clinical diagnosis of lichen planus correlated with the biopsy findings in 80% of the cases and with pemphigoid in 60%. Definitive diagnosis was rendered to 80% of the gingival biopsies submitted. Negative cases of direct IF presenting as DG had significant pathology, such as dysplasia and carcinoma, which would have been otherwise missed if H & E studies had not been performed. Conclusions: This study has the largest cohort of patients with DG suspected of VBD reported in the literature. The patients were predominantly females who had most often been seen by a periodontist. The definitive diagnosis of DG was most accurately achieved when H & E along with two biopsies for direct IF studies were submitted for testing. H & E studies were particularly important for definitive diagnosis of negative cases. Oral lichen planus was the most common disease presenting as DG, which is consistent with recent studies. Systemic connective tissue disorders that present as DG at initial clinical examination require direct IF and serum studies for a conclusive diagnosis. Clinical pathologic correlation, including history, presentation, H & E, and direct IF studies, are essential in establishing a definitive and differential diagnosis for cases presenting with DG. J Periodontol 2012;83:1270-1278.

The styloid process refers to a mineralized styloid ligament of the temporal bone that usually appears (in different forms and lengths) on panoramic radiographs. This study sought to evaluate panoramic radiographs to determine the prevalence and clinical significance of elongated calcified styloid processes. For this study, panoramic radiographs from 1,000 dental patients were evaluated. Each styloid process length was measured and its pattern of calcification was assessed as elongated (that is, uninterrupted styloid calcification), pseudoarticulated (a single joint appearing as an articulated styloid process), or segmented (an interrupted calcified styloid process). Calcified styloid processes longer than 30 mm were considered to be elongated and were used for this study; 220 panoramic radiographs (22%) revealed such elongated processes. This retrospective study indicated that there is no clinical significance when elongated styloid processes are found coincidentally.

The etiology of salivary gland injury in primary Sjögren’s disease is not well understood. We have previously described a mouse model of Sjögren’s disease, IL-14α transgenic (IL14αTG) mice, which reproduces many of the features of the human disease. We now demonstrate a critical role for lymphotoxin α (LTA) in the pathogenesis of Sjögren’s disease in IL14αTG mice. IL14αTG mice express LTA mRNA in their salivary glands and spleen and produce soluble LTA protein in their salivary secretions. When IL14αTG mice were crossed with LTA−/− mice, the IL14αTG.LTA−/− mice retained normal salivary gland secretions and did not develop either lymphocytic infiltration of their salivary glands or secondary lymphomas. However, both IL14αTG and IL14αTG.LTA−/− mice produced similar amounts of IFN-α and had similar deposition of autoantibodies in their salivary glands. Both IL14α and IL14α/LTA−/− mice had similar B cell responses to T-dependent and T-independent Ags, L-selectin expression, and expression of RelA, RelB, and NF-κB2 in their spleens. These studies suggest that LTA plays a critical role in the local rather than systemic inflammatory process of Sjögren’s disease. Furthermore, local production of soluble LTA in the salivary glands of IL14αTG mice is necessary for the development of overt Sjögren’s disease. Autoantibody deposition alone is not sufficient to produce salivary gland dysfunction. We also demonstrate that LTA is increased in the salivary gland secretions and sera of patients with Sjögren’s disease, further strengthening the biological relevance of the IL14αTG model to understanding the pathogenesis of human disease.

Desmoplastic fibroma is a rare and locally aggressive lesion that affects the long bone and the jaw bones. Mandibular bone involvement has been mostly reported in the posterior segment; anterior region presentation is rare. This case report highlights the diagnosis, management and treatment of a midline mandibular involvement. It includes a literature review.

To evaluate the role of interleukin 14 alpha (IL-14a) in Sjogren's syndrome (SS), we evaluated the expression of IL-14a in the peripheral blood lymphocytes (PBL) of patients with primary and secondary SS and normal controls by quantitative RT-PCR. In addition, transgenic IL-14a mice were analyzed from 6 weeks of age to death for both histological and immunological features of Sjogren's disease. Patients with both primary and secondary Sjogren's syndrome expressed IL-14a at statistically higher levels in their peripheral blood compared to normal controls matched for age, sex and ethnic group. Transgenic mice in which IL-14a expression was increased constitutively were previously demonstrated to develop hypergammaglobulinemia, autoantibodies, infiltration of the parotid glands with lymphocytes, mild immune-complex mediated renal disease and large B cell lymphoma. In this paper we expand these observations to demonstrate that these mice develop all the clinical and immunological features of primary Sjogren's disease in the same relative time frame as patients with primary Sjogren's disease: stage 1-early hypergammaglobulinemia and autoantibody production, stage 2-decreased salivary gland function with early lymphocytic infiltration of the submandibular glands only, but antibody deposition in the submandibular and parotid glands, stage 3-lymphocytic infiltration of the submandibular, parotid and lacrimal glands with B and T lymphocytes and plasma cells along with interstitial lung disease and mild renal disease, and stage 4-large B cell lymphoma. Thus IL-14a is important in the pathophysiology of Sjogren's disease. The IL-14a transgenic mouse is a novel animal model that can be utilized to understand the pathophysiology of Sjogren's disease.

Advances in health care and pharmacotherapeutics have led to a growing aging population living with complex medical conditions. These changes are apparent in patients presenting for treatment at dental schools. This study assessed the medical profile of patients seeking treatment at the School of Dental Medicine, State University of New York at Buffalo. Medical records of 1,041 consecutive patients who presented for comprehensive dental care at the school were retrospectively reviewed. The demographic data, medical status, and use of medications from the charts were analyzed. The mean age of the patients was 52 (SD+/-18), and the female to male ratio was 1.2:1. More than half of the patients had one or more systemic illnesses or were taking medication. The results of this study reflect the medical complexity of the growing aging population. The dental school curriculum should address the needs for management of the growing number of medically complex patients.

Background Existing clinical trials have shown that topical corticosteroids are often effective in the management of oral lichen planus (OLP). However, tacrolimus has recently been shown to be an effective treatment of OLP. Objective To compare the effectiveness of clobetasol and tacrolimus in the topical management of OLP. Study design In this randomized comparative double-blind study, 30 consecutive patients with oral lesions consistent clinically and histologically with OLP were recruited.The patients were divided into 2 groups to receive clobetasol 0.05% or tacrolimus 0.1% ointment and were treated for 6 weeks. Results The profiles of mean lesion sizes and mean pain measures did not differ between the tacrolimus and clobetasol treatment groups. Conclusion We found tacrolimus to be as useful as clobetasol in treatment of OLP. We believe that up-to-date evidence indicates the effectiveness of tacrolimus in treating OLP.

Leiomyoma is a benign smooth muscle tumor that usually is found in the uterus, gastrointestinal tract, or skin. It appears infrequently in the oral cavity. Intraosseous leiomyomas are rare; to date, only 14 cases have been reported in the English-language literature. Gnathic leiomyoma occurs more commonly in the posterior mandible as an asymptomatic swelling with variable radiographic appearance. Microscopically, 53% of gnathic leiomyomas have a prominent vascular component that warrants a diagnosis of angiomyoma. Surgical excision is the treatment of choice. This article describes the clinical-pathological features of an exceptional intraosseous angiomyoma of the mandible.

Mandibular lingual bone depressions are considered to be developmental anomalies and most clinicians are familiar with the posterior variant (known as Stafne's bone cavity) that occurs in lingual mandibular molar regions, adjacent to the submandibular gland and below the mandibular canal. The anterior variant of the mandibular lingual bone depression is an asymptomatic bone cavity that occurs adjacent to the sublingual gland in the anterior mandible. Radiographically, it appears as a well-corticated radiolucency that retains a normal trabecular pattern internally. CT imaging is diagnostic and avoids surgical and sialographic procedures. This article reviews radiographic and CT features of a case involving the anterior variant of mandibular lingual bone depression.

Mucous membrane pemphigoid (MMP) is a heterogeneous group of autoimmune, chronic inflammatory ubepithelial vesiculobullous disorders, predominantly affects the mucous membranes of the oral cavity and eyes of the elderly population. Oral manifestations of pemphigoid include desquamative gingivitis, ulcers, erythematous patches, erosions, vesicles and bullae located on the attached gingiva, palate, buccal mucosa, labial mucosa, and tongue. Diagnosis is based on history, clinical features and a biopsy stained with hematoxylin and eosin (H&E), and also direct and indirect immunofluorescence. Topical and systemic corticosteroids are the most commonly used medications for managing pemphigoid. Recently, topical tacrolimus has been successfully used in the treatment of ocular and skin pemphigoid. In this report we present a patient with longterm recalcitrant MMP that did not respond to conventional treatment but as treated successfully with tacrolimus ointment.

Pyostomatitis vegetans (PV) is a rare, benign, and chronic disorder of the oral soft tissues characterized by the presence of multiple pustules with an erythematous base. PV is considered a highly specific clinical marker for inflammatory bowel disease (IBD). The first reports of PV were documented by Hallopeau in 1898, who described 2 cases with unusual pustular dermatosis and oral lesions that he called pyodermite vegetante. The term pyostomatitis vegetans was coined by McCarthy in 1949, who believed that it was a variant of pyodermite vegetante. Since McCarthy’s report in 1949, approximately 50 cases have been published in the literature. In this report, we present a typical case of PV.

Cheilitis glandularis (CG) is a rare inflammatory salivary gland disease that usually affects the lips. Although the etiology of CG is still unknown, it is believed to be a hereditary disease with an autosomal dominant pattern of inheritance. Three clinical presentations of CG are described in the literature: simple, superficial suppurative, and deep suppurative. A case of deep suppurative CG that extended to the buccal mucosa has been previously reported as suppurative stomatitis glandularis (SSG). Here we report a case of SSG in a 64-year-old white female with a history of bilateral renal transplants for adult polycystic kidney disease, who presented with painful swollen lips and bilateral buccal mucosal lesions. The diagnosis and management of the case is discussed. To the best of our knowledge, this is the second report of SSG, a rare condition affecting the minor salivary glands in the oral cavity.

A case involving a 17-year-old girl with a large erupted odontoma associated with a deeply impacted mandibular molar is reported. The molar, which previously had been displaced to the border of the mandible, erupted successfully three years after surgical removal of the odontoma. A review of the literature presents guidelines for treating similar cases.

Pregnancy results in physiologic changes in almost all organ systems in the body mediated mainly by female sex hormones. Physiologic changes of pregnancy influence the dental management of women during pregnancy. Understanding these normal changes is essential for providing quality care for pregnant women. This review article briefly discusses the cardiovascular, respiratory, gastrointestinal, urogenital, endocrine, and oral physiologic changes that occur during normal gestation. A summary of current scientific knowledge of ionizing radiation is presented. Information about the compatibility, complications, and excretion of the common drugs during pregnancy is provided. Drugs and their usage during breast-feeding are also discussed. Guidelines for the management of a pregnant patient in the dental office are summarized.