Photobiomodulation of gingival lesions resulting from autoimmune diseases: systematic review and meta-analysis.

OBJECTIVES: To evaluate the effects of photobiomodulation (PBM) in gingival lesions resulting from autoimmune diseases; to compare PBM and topical corticosteroid (CS) treatment; and to assess PBM outcome over time of follow-up. MATERIALS AND METHODS: A comprehensive electronic search was performed in four electronic databases. Treatment effects were measured through visual analog scale of pain (VAS) and clinical evolution of lesion (Thongprasom scale for oral lichen planus (OLP)). Meta-analysis was performed to compare PBM with topical corticosteroid treatment and to evaluate PBM effect over time of follow-up. RESULTS: Seventeen studies were included in this review, of which six were used for the meta-analysis. Meta-analysis results showed no significant differences between PBM and topical CS in pain reduction at baseline (MD = 0.20, 95% CI = - 0.92, 1.32, p = 0.72) and 60-day follow-up (MD = 0.63, 95% CI = - 3.93, 5.19, p = 0.79); however, VAS showed significant pain reduction when compared before and after PBM at 30-day (MD = - 3.52, 95% CI = - 5.40, - 1.64, p = 0.0002) and 60-day (MD = - 5.04, 95% CI = - 5.86, - 4.22, p < 0.00001) follow-up. Thongprasom clinical scale for OLP also showed significant improvement at 30-day follow-up (MD = - 2.50, 95% CI = - 2.92, - 2.08, p < 0.00001) after PBM. CONCLUSION: PBM led to significant reduction of pain and clinical scores of the lesions, not having shown significant differences when compared to topical CS. CLINICAL RELEVANCE: PBM has been used in the treatment of autoimmune gingival lesions, but so far there is little strong evidence to support its use.

Toxicity and Cosmetic Outcome of Breast Irradiation in Women with Breast Cancer and Autoimmune Connective Tissue Disease: The Role of Fraction and Field Size.

PURPOSE: Hypofractionation has historically been underused among breast cancer patients with connective tissue diseases given a theoretical risk of increased toxicity and their overall underrepresentation in clinical trials that established hypofractionation as standard of care. We aim to compare the rates of toxicity in patients with autoimmune connective tissue diseases treated with conventionally fractioned radiation therapy (CF-RT) and hypofractionated radiation therapy (HF-RT) including accelerated partial breast irradiation. METHODS: A total of 1983 patients treated with breast conservation between 2012 and 2016 were reviewed for diagnosis of autoimmune disease. Univariate analysis using binary logistic regression was performed to evaluate the effect of disease and treatment variables on acute and late toxicity. Multivariate analyses using Cox regression models were used to evaluate the independent associations between covariates and the primary end points. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for reach risk group. RESULTS: Ninety-two patients with autoimmune disease were identified. Median follow-up was 59 months. Of the patients 35% received CF-RT and 65% received HF-RT, of whom 70% received whole breast radiation (WBI) without regional nodal irradiation, 12% received WBI with regional nodal irradiation, and 18% received accelerated partial breast radiation. Patients who received CF-RT were significantly more likely to have autoimmune disease (AD) symptoms (78% vs 37%, P <.001), to be managed on disease-modifying antirheumatic drugs (DMARDs; 41% vs 15%, P = .013), and to have active autoimmune disease (84% vs 43%, P <.001). On multivariate analysis, HF-RT was associated with a significantly decreased odds of acute and late grade 2/3 toxicity compared with CF-RT fractionation (acute: OR 0.200, 95% CI 0.064-0.622, P = .005; late: OR 0.127, 95% CI 0.031-0.546, P = .005). CONCLUSIONS: Hypofractionation including accelerated partial-breast irradiation is associated with less acute or late grade 2/3 toxicity in this population.

Orbital Radiation Therapy in Thyroid Eye Disease.

PURPOSE: To review the current literature summarizing the state of knowledge on the use of orbital radiation therapy (ORT) in thyroid eye disease. METHODS: A systematic review and analysis of the literature were performed. MEDLINE/PubMed, Cochrane Library databases, SCOPUS, and recent relevant journal articles were searched. RESULTS: Thyroid eye disease is an autoimmune disorder that has the propensity to affect multiple orbital tissues and can cause permanent vision loss. In moderate to severe disease, treatment may be warranted and can include multiple therapeutic modalities. Orbital radiation therapy is frequently used in this setting and may act to break the inflammatory cycle of glycosaminoglycan production and deposition. There has been a wealth of data regarding the effectiveness of ORT in thyroid eye disease resulting in the publication of treatment algorithms and management guidelines; however, there continues to be a lack of conformity among experts on the exact role of ORT in thyroid eye disease. CONCLUSION: The multiple different thyroid eye disease classification schemes and the concurrent use of other therapeutic modalities challenge the interpretation of studies evaluating the effectiveness of thyroid eye disease. Despite these limitations, the current literature indicates that ORT is generally safe and well tolerated. Orbital radiation therapy may have a modest effect on motility and proptosis early in the disease process. It is unclear whether ORT leads to improved quality of life. There are some data to support the use of ORT to prevent compressive optic neuropathy.

The consequences of UV-induced immunosuppression for human health.

Exposure to UV radiation can cause suppression of specific immune responses. The pathways leading to the down-regulation are complex, starting from the absorption of UV photons by chromophores in the skin and ending with local and systemic changes in immune mediators, the generation of T and B regulatory cells and inhibition of effector and memory T cell activation. The consequences for human health are thought to be both beneficial and adverse. The former are illustrated by protection against polymorphic light eruption, and possible protection against T cell-mediated autoimmune diseases and asthma. The latter are illustrated by skin cancer, cutaneous lupus erythematosus and infectious diseases including vaccination. Many outstanding questions remain in this rapidly developing and controversial area, not least what advice to give the general public regarding their sun exposure. While considerable advances have been made in the development of strategies that preserve the health benefits of sunlight exposure and decrease its detrimental effects, further research is required before optimal levels of protection are achieved.

Autoimmunity in differentiated thyroid cancer: significance and related clinical problems.

Coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune diseases could represent a mere coincidence due to the frequent occurrence of autoimmunity, but there may also be a pathological and causative link between the two conditions. The coincidence of DTC with Hashimoto's disease has been variably reported at between 0.5 and 22.5% and of DTC with Graves' disease between 0 and 9.8%. In this review available evidence for thyroid autoimmunity in DTC is summarized and it is concluded that thyroid cancer does coexist with thyroid autoimmunity, implying that patients treated for autoimmune thyroid diseases should have a careful follow-up. Furthermore, the presence of thyroglobulin antibodies (TgAb) in patients with DTC may limit the use of serum thyroglobulin as a tumor marker due to methodological problems in the determination of serum thyroglobulin. However, in such cases serial TgAb measurements may be used as a surrogate marker for recurrence of thyroid cancer during the long-term monitoring of DTC patients.

Unintended benefits of immunosupression on autoimmune disease due to chemoradiation therapy for head and neck cancer.

The immune system is an important factor in the host's defenses against cancer. Immunosupression by radiation and/or chemotherapy is often associated with systemic and hematologic complications, opportunistic infections, and the development of malignancies, but immunosupression can also have beneficial effects, which are sometimes incidental. We report 2 patients with autoimmune diseases where immunosupression had beneficial effects. The first case is about a patient with carcinoma of the tonsil, with severe rheumatoid arthritis, who was treated with chemoradiation, which resulted in remission of his arthritis. The second case is about a patient with severe atopic eczema who was on long-term treatment with psoralen and ultraviolet A radiation and azathioprine; the patient developed metastatic carcinoma of the lip, which was treated with surgery and radiation that resulted in complete remission of his eczema.

Radioiodine treatment in autoimmune hyperthyroidism: analysis of outcomes in relation to dosage.

BACKGROUND: Controversy exists regarding the optimal dose of radioiodine ((131)I) therapy in autoimmune hyperthyroidism (i.e., Graves' Disease). METHODS: In order to evaluate the efficacy and safety of high dose (131)I therapy in autoimmune hyperthyroidism, a retrospective review of patients who received (131)I therapy for Graves' disease from 1980 to 2000 in the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City was carried out. RESULTS: The study population consisted of 596 autoimmune hyperthyroid patients with a mean age of 35 years. The mean follow-up period was 10.31 +/- 2.37 years. Remission of hyperthyroidism occurred in 81.9%, persistent hyperthyroidism was recorded in 14.4% and recurrence in 3.7%. (131)I doses of 5-9 mCi (185-333 MBq) and > or =20 mCi (> or =740 MBq) were associated with remission rates of 65.5% and 87.7% respectively. Remission occurred earlier and more often with high doses of (131)I. The high-dose group (20-30 mCi [740-1110 MBq]) had the lowest rate of persistence (9.7, 27.5 and 34.3%, for 20-30 [740-1110 MBq], 10-14 [370-518 MBq] and 5-9 [185-333 MBq] mCi, respectively p <0.05) and hypothyroidism occurred earlier in this group (p = 0.05). CONCLUSIONS: Remission of autoimmune hyperthyroidism is more likely with doses of 20-30 mCi (740-1110 MBq).

Effectiveness of radioiodine (131-I) as definitive therapy in patients with autoimmune and non-autoimmune hyperthyroidism.

We evaluated the outcome of radioiodine (RAI) therapy in 100 consecutive patients treated in the period 2000-2001 for hyperthyroidism due to Graves' disease (GD), toxic adenoma (TA) and toxic multinodular goiter (TMG). Thyroid function was measured before and after therapy every 3-6 months up to 3 yr. Three years after therapy, 75% of TA patients were euthyroid, 18.7% were hypothyroid and 6.3% hyperthyroid. Of the TMG patients, 62.2% were euthyroid, 18.9% were hypothyroid and 18.9% hyperthyroid. In GD patients euthyroidism was achieved in 12.9% of the patients, hypothyroidism in 74.2% and hyperthyroidism persisted in 12.9%. Definitive hypothyroidism was significantly higher in GD (p<0.0001) than in TA and TMG patients. Overall, positive effect of RAI (definitive hypothyroidism or euthyroidism) was very high: 93.7% in TA, 81.1% in TMG and 87.1% in GD patients. Thyroid volume reduction was observed in all patients, but was higher in GD patients (mean reduction of 76%) and in TA patients (mean nodule reduction of 69%). In TMG, mean reduction was of 32%. The median activity of RAI received by the 86 cured patients was 555 MBq (15 mCi) compared to 407 Mbq (11 mCi) received by the 14 patients who remained hyperthyroid. No influence was found between outcome and clinical parameters at the moment of 131-I therapy. In conclusion, our results indicate that RAI therapy is highly effective and safe for the control of hyperthyroidism.

Total lymphoid irradiation: new therapeutic option for refractory giant cell myocarditis.

Idiopathic giant cell myocarditis (GCM) is believed to be a T-lymphocyte-mediated autoimmune disease. Some patients with GCM have a dramatic clinical response to anti-T-cell immunosuppression. However, this response is not uniform and patients often deteriorate rapidly and need a cardiac transplantation within months of diagnosis. Following cardiac transplantation, GCM may recur in the graft but is usually mild and responds to augmentation of immunosuppression. This report is the first description of total lymphoid irradiation (TLI) for the treatment of GCM, which was used in a patient who developed an exceptionally early and severe recurrence of GCM in the cardiac graft that remained refractory to heightened immunosuppression for 4 months. Clinical and histologic remission followed a course of TLI and was maintained for 1 year despite a gradual decrease in immunosuppression. This novel treatment should be considered in all patients with GCM who do not have histologic remission with the currently employed anti-T-cell immunosuppression.

Effect of extended exposure to low-dose radiation on autoimmune diseases of immunologically suppressed MRL/MpTn-gld/gld mice.

The purpose of this paper is to analyze the relationship between alterations of splenic T-cell subpopulations and the amelioration of autoimmune diseases of MRL/MpTn-gld/gld mice (MRL/gld mice) after extended exposure to low-dose radiation. After the onset of disease, 4-month-old MRL/gld mice were exposed to doses of 0.05, 0.2, and 0.5 Gy/day for 4 weeks (5 days/week), for total doses of 1, 4, and 10 Gy, respectively. The MRL/gld mice that were irradiated with 0.2 and 0.5 Gy/day showed an obvious decrease in the proportion of splenic CD4(-)CD8(-) T cells and remission of their autoimmune diseases. After the last irradiation, apoptotic cells were found in the white pulp of the spleen of the MRL/gld mice irradiated with 0.2 Gy/day, but not in the MRL/MpJ-+/+ mice (MRL/wild mice), which experienced a similar treatment. Before the onset of disease, 3-month-old MRL/gld mice subjected to 0.2 Gy/day showed a decrease in the proportion of splenic CD4(-)CD8(-) T cells and less remission of their autoimmune diseases than the 4-month-old mice. These results suggest that the accumulated CD4(-)CD8(-) T cells are more sensitive to radiation than other T-cell subpopulations, and that decreasing CD4(-)CD8(-) T cells with extended exposure to low-dose radiation leads to the amelioration of autoimmune disease.

Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome.

Immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX, OMIM 304790) is a rare, recessive disorder resulting in aggressive autoimmunity and early death. Mutations in FOXP3 have been identified in 13 of 14 patients tested. Research in the mouse model, scurfy, suggests that autoimmunity may stem from a lack of working regulatory T cells. We review published reports regarding the genetics, clinical features, immunology, pathology, and treatment of IPEX. We also report three new patients who were treated with long term immunosuppression, followed by bone marrow transplantation in two. IPEX can be differentiated from other genetic immune disorders by its genetics, clinical presentation, characteristic pattern of pathology, and, except for high IgE, absence of substantial laboratory evidence of immunodeficiency. While chronic treatment with immunosuppressive drugs may provide temporary benefit for some patients, it does not cause complete remission. Remission has been observed with bone marrow transplantation despite incomplete engraftment, but the long term outcome is uncertain.

Treatment of autoimmune diseases by hematopoietic stem cell transplantation.

Remarkable advances have been made in bone marrow transplantation (BMT), which now has become a powerful strategy for the treatment of leukemia, aplastic anemia, congenital immunodeficiency disorders, and autoimmune diseases. Using various animal models, allogeneic BMT has been found to be useful in the treatment of autoimmune diseases. In MRL/lpr mice, which are radiosensitive (<8.5 Gy) and are an animal model for autoimmune disorders, conventional BMT resulted in only transient effects; the manifestations of the autoimmune diseases recurred 3 months after BMT. However, the combination of BMT plus bone grafts (to recruit donor stromal cells) was capable of preventing the recurrence of autoimmune diseases in MRL/lpr mice. This strategy was found to be ineffective in the treatment of MRL/lpr mice that had developed autoimmune diseases, because these mice were more sensitive to the effects of radiation after the onset of lupus nephritis due to uremic enterocolitis. We have recently discovered a safer strategy for treatment of autoimmune diseases, which includes fractionated irradiation (5.5 Gy x 2) (day -1) followed by portal venous injection (day 0) plus intravenous injection (day 5) of donor unfractionated bone marrow cells. We successfully treated autoimmune diseases in MRL/lpr mice using this strategy; 100% of MRL/lpr mice treated in this fashion survive >1 year after treatment. We identified the mechanisms underlying the components of this approach and have found that stromal cells play a crucial role in successful BMT. In this review, the conditions essential for successful allogeneic BMT are discussed.

[Radioiodine (131I) as the only treatment of hyperthyroidism. Results of 10 years of experience]. / Radioiode (131I) comme seul traitement de l'hyperthyroïdie. Résultats d'une expérience de 10 années.

This work present the results of the use of 131I, as first line and only, antithyroid treatment, applied to 120 patients suffering from autoimmune hyperthyroidism, compared to 64 patients with toxic goiter and adenoma. The diagnostic weight of the determination of the various antithyroid antibodies was assessed in the identification of autoimmune hyperthyroidism, for which TRAb and TPO Ab are the most significant. The evolution after treatment of a preexisting ophthalmopathy (i.e. Graves'disease) was never found to be alarming and in most cases regularly improved with time. A single case (out of 72) of autoimmune hyperthyroidism with no preexisting sign developed a severe ophthalmopathy after treatment, which was well controlled thereafter. Mean cumulated 131I doses to control hyperthyroidism were 22.8 mCi for toxic goiter, 21.6 mCi for adenoma, 14.1 mCi for autoimmune hyperthyroidism and 16.7 mCi for Graves'disease. Post 131I hypothyroidism was found in 28.2% of toxic goiters, 12.1% of adenomas, 66% of autoimmune hyperthyroidisms and 70% of Graves'disease. No relapse was observed after treatment. A surgical indication was proposed for cases requiring more than two 131I doses to control hyperthyroidism.

Low-dose splenic irradiation in the treatment of immune thrombocytopenia in HIV-infected patients.

PURPOSE: To determine the effect of low-dose splenic irradiation on severe Zidovudine-resistant, HIV-1-associated thrombocytopenia (HAT). METHODS AND MATERIALS: Between September 1994 and October 1996, 17 patients were included in a prospective study. The patients met the following criteria for inclusion: hemorrhagic symptoms or a platelet count below or equal to 50 x 10(9)/l and normal numbers of megakaryocytes on bone aspiration. The mean baseline platelet count was 20.3 (+/- 14.4) x 10(9)/l; four patients had a platelet count inferior to 10 x 10(9)/l. Splenic volume was defined by ultrasonography. A total dose of 9 Gy was given using an isocentric parallel pair field technique. RESULTS: One month after the end of treatment six patients had a significant rise in their platelet count. Clinically, hemorrhagic symptoms stopped for all patients that were symptomatic. Unfortunately, duration of response was short because for one patient only the platelet count remains stable with a follow-up of 6 months. All patients are alive and in recent evaluation, with four out of eight patients receiving a combination of antiretroviral therapy had a platelet count above 50 x 10(9)/l. CONCLUSION: Our results are disappointing concerning the duration of response, especially comparatively to those reported in autoimmune thrombocytopenia. Mechanisms of HAT are more complex, and megakaryocytes' infection may play an important role. Splenic irradiation should be considered as palliative treatment for the minority of patients with severe bleeding that does not respond to standard medical treatment.

Splenic irradiation for chronic autoimmune thrombocytopenic purpura in patients with contra-indications to splenectomy.

We treated by splenic irradiation eight patients with chronic idiopathic thrombocytopenic purpura (ITP, seven cases) or secondary autoimmune thrombocytopenic purpura (one case) who had contra-indications to splenectomy. A total dose of 15 Gy was delivered to the spleen, with left kidney protection. One patient had a good durable response (> 1 year); two patients had a good transient response (of 3 months duration) but they responded again to a second course of irradiation; two patients had only partial response, but have required no other treatments for 2 years; the three remaining patients had no response. Side-effects were minor. Therefore splenic irradiation appears to be a therapeutic option in patients with chronic ITP who have contra-indications to splenectomy.

Basic aspects of neuroimmunology as they relate to immunotherapeutic targets: present and future prospects.

The neurological diseases with definite or putative immune pathogenesis include myasthenia gravis; Lambert-Eaton myasthenic syndrome; IgM monoclonal anti-myelin-associated glycoprotein-associated demyelinating polyneuropathy; Guillain-Barré syndrome; chronic inflammatory demyelinating polyneuropathy; multifocal motor neuropathy with or without GM1 antibodies; multiple sclerosis; inflammatory myopathies; stiff-man syndrome; autoimmune neuromyotonia; paraneoplastic neuronopathies and cerebellar degeneration; and neurological diseases associated with systemic autoimmune conditions, vasculitis, or viral infections. The events that lead to these autoimmune diseases are not clear but the following sequential steps are critical: (a) the breaking of tolerance, a process in which cytokines, molecular mimicry, or superantigens may play a role in rendering previously anergic T cells to recognize neural autoantigens; (b) antigen recognition by the T-cell receptor complex and processing of the antigen via the major histocompatibility complex class I or II; (c) costimulatory factors especially B7 and B7-binding proteins (CD28, CTLA-4) and intercellular adhesion molecule (ICAM)-1 and its leukocyte function-associated (LFA)-1 ligand; (d) traffic of the activated T cells across the blood-brain or blood-nerve barrier via a series of adhesion molecules that include selectins, leukocyte integrins (LFA-1, Mac-1, very late activating antigen [VLA]-4) and their counterreceptors (ICAM-1, vascular cell adhesion molecule [VCAM]) on the endothelial cells; and (e) tissue injury when the activated T cells, macrophages, or specific autoantibodies find their antigenic targets on glial cells, myelin, axon, calcium channels, or muscle. In designing specific immunotherapy, the main players involved in every step of the immune response need to be considered. Targets for specific therapy in neurological diseases include agents that (a) interfere or compete with antigen recognition or stimulation, (b) inhibit costimulatory signals or cytokines, (c) inhibit the traffic of the activated cells to tissues, and (d) intervene at the antigen recognition sites in the targeted organ. The various immunomodulating procedures and immunosuppressive drugs currently used for nonselective neuroimmunotherapy are discussed in the context of their interference with the above-described immune mediators.

Uniocular fields of fixation in thyroid eye disease.

Immunosuppressive therapy is well established in the treatment of thyroid eye disease (TED). The best response has been observed in those with active (wet phase) disease of short duration. A prospective study was designed to observe the effects of orbital radiotherapy and oral immunosuppression on patients with TED, and to assess whether any pre-treatment parameters were predictive of the outcome. Significant improvements in uniocular fields of fixation (UFOF) and in the Mourits' disease activity scale were seen after treatment. The degree of improvement in UFOF was positively correlated with the level of initial disease activity. The use and technique of UFOF in assessing disease phase and activity are discussed.