ABSTRACT
Immunogenicity of SARS-CoV-2 vaccines in kidney transplant recipients is limited, resulting in inadequately low serological response rates and low immunoglobulin (Ig) levels, correlating with reduced protection against death and hospitalization from COVID-19. We retrospectively examined the time course of anti-SARS-CoV-2 Ig antibody levels after up to five repeated vaccinations in 644 previously nonresponding kidney transplant recipients. Using anti SARS-CoV-2 IgG/IgA ELISA and the total Ig ECLIA assays, we compare antibody levels at 1 month with levels at 2 and 4 months, respectively. Additionally, we correlate the measurements of the used assays. Between 1 and 2 months, and between 1 and 4 months, mean anti-SARS-CoV-2 Ig levels in responders decreased by 14% and 25%, respectively, depending on the assay. Absolute Ig values and time course of antibody levels and showed high interindividual variability. Ig levels decreased by at least 20% in 77 of 148 paired samples with loss of sufficient serological protection over time occurring in 18 out of 148 (12.2%). IgG ELISA and total Ig ECLIA assays showed a strong positive correlation (Kendalls tau=0.78), yet the two assays determined divergent results in 99 of 751 (13.2%) measurements. IgG and IgA assays showed overall strong correlation but divergent results in 270 of 1.173 (23.0%) cases and only weak correlation of antibody levels in positive samples. Large interindividual variability and significant loss of serological protection after 4 months supports repeated serological sampling and consideration of shorter vaccination intervals in kidney transplant recipients.
ABSTRACT
Mortality from COVID-19 among kidney transplant recipients (KTR) is high, and their response to three vaccinations against SARS-CoV-2 is strongly impaired. We retrospectively analyzed serological response of up to five doses of SARS-CoV-2 vaccine in KTR from December 27, 2020, until December 31, 2021. Particularly, the influence of different dose adjustment regimens for mycophenolic acid (MPA) on serological response to fourth vaccination was analyzed. In total, 4.277 vaccinations against SARS-CoV-2 in 1.478 patients were analyzed. Serological response was 19.5% after 1.203 basic immunizations, and increased to 29.4%, 55.6%, and 57.5% in response to 603 third, 250 fourth and 40 fifth vaccinations, resulting in a cumulative response rate of 88.7%. In patients with calcineurin inhibitor and MPA maintenance immunosuppression, pausing MPA and adding 5 mg prednisolone equivalent before the fourth vaccination increased serological response rate to 75% in comparison to no dose adjustment (52%) or dose reduction (46%). Belatacept-treated patients had a response rate of 8.7% (4/46) after three vaccinations and 12.5% (3/25) after four vaccinations. Except for belatacept-treated patients, repeated SARS-CoV-2 vaccination of up to five times effectively induces serological response in kidney transplant recipients. It can be enhanced by pausing MPA at the time of vaccination.
ABSTRACT
Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from autoimmune patients suggest that temporary MPA hold might significantly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine during temporary (5 weeks) MPA hold to 29 kidney transplant recipients, who had not mounted a humoral immune-response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus neutralizing capacity. Interestingly, 21/25 (84%) CNI-treated patients responded, but only 1/4 Belatacept-treated patients. In line with humoral responses, counts and relative frequencies of spike receptor binding domain (RBD) specific B cells were significantly increased on day 7 after vaccination, with an increase in RBD specific CD27++CD38+ plasmablasts. Whereas overall proportions of spike-reactive CD4+ T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67+ and in vivo activated PD1+ T cells significantly increased after re-vaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, MPA hold was safe and augmented all arms of immunity during booster vaccination, suggesting its implementation in vaccination protocols for clinically stable transplant recipients.
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An allergy skin test is used to diagnose certain allergies by identifying sensitized allergens. In other words, it is a test for patients who are already sensitized to certain allergens. Because of the prevailing perception that beta-lactam allergy can be dangerous and potentially lethal, the intradermal test has long been routinely performed before use to screen beta-lactam allergy in Korea. The prevalence of penicillin allergy is estimated to be 1% to 2%. However, only 14% of the subjects with perceived penicillin allergy is considered to have true penicillin allergy. Moreover, it is difficult to justify performing a skin test on subjects who are very unlikely to be sensitized to beta-lactam, such as those who never used beta-lactam or never experienced allergy after previous use of beta-lactam.Therefore, allergists recommend beta-lactam skin testing in those who have allergy after the use of beta-lactam. Nevertheless, many hospitals in Korea are conducting routine skin tests on patients regardless of a history of beta-lactam allergy, which are not clinically validated but consume considerable human and material resources. False-positive results can consequently result in inappropriate labeling of beta-lactam allergy, leading to the unnecessary restriction of medication prescriptions and the increase in medical expenses. Herein, the drug allergy working group affiliated with the Korean Academy of Asthma, Allergy, and Clinical Immunology announces an expert opinion on the preuse beta-lactam skin test for subjects without a history of beta-lactam allergy based on the objective evidence from the literature and clinical relevance.
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BackgroundAccumulating evidence suggests that solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness towards standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protection of this vulnerable group. MethodsIn line with recent recommendations, a third dose of either heterologous ChAdOx1 (AstraZeneca) or homologous BNT162b2 (BioNTech) was administered to 25 kidney transplant recipients (KTR) without humoral response after 2 doses of BNT162b2, followed by analysis of serological responses and vaccine-specific B- and T-cell immunity. Results9/25 (36%) KTR under standard immunosuppressive treatment seroconverted until day 27 after the third vaccination, while one patient developed severe COVID-19 infection immediately after vaccination. Cellular analysis seven days after the third dose showed significantly elevated frequencies of viral spike protein receptor binding domain specific B cells in humoral responders as compared to non-responders. Likewise, portions of spike-reactive CD4+ T helper cells were significantly elevated in seroconverting patients. Furthermore, overall frequencies of IL-2+, IL-4+ and polyfunctional CD4+ T cells significantly increased after the third dose, whereas memory/effector differentiation remained unaffected. ConclusionsOur data suggest that a fraction of transplant recipients benefits from triple vaccination, where seroconversion is associated with quantitative and qualitative changes of cellular immunity. At the same time, the study highlights that modified vaccination approaches for immunosuppressed patients still remain an urgent medical need. Significance statementProtection of solid organ transplant recipients against SARS-Cov-2 by vaccination remains an unmet need given the low immunogenicity of available vaccines in the presence of immunosuppression. Administration of a third dose to 25 kidney transplant recipients (KTR) resulted in seroconversion in 36% of patients, associated with significant quantitative and functional changes within the spike-antigen-specific B-cell- and CD4+ T-helper cell compartment. Our data support the need for individual humoral monitoring of immunosuppressed individuals after vaccination as well as continued efforts to adapt vaccination protocols for this at-risk group.
ABSTRACT
Patients with kidney failure are at increased risk during the COVID-19 pandemic and effective vaccinations are needed. It is not known how efficient mRNA vaccines mount B and plasma cell responses in dialysis patients (DP) or kidney transplant recipients (KTR) compared to healthy controls (HC). We studied humoral and B cell responses of 25 HC, 44 DP and 40 KTR. Markedly impaired anti-BNT162b2 responses were identified among KTR and DP compared to 100% seroconversion in HC. In DP, the response was delayed (3-4 weeks after boost) and reduced with anti-S1 IgG positivity in 31 (70.5%) and anti-S1 IgA in 30 (68.2%) of 44, respectively. In contrast, KTR did not develop IgG response except one patient who had prior unrecognized infection and developed anti-S1 IgG. The majority of antigen-specific B cells (RBD+) were identified in the plasmablast or post-switch memory B cell compartments in HC, whereas these RBD+ B cells were enriched among pre-switch and naive B cells from DP and KTR. Single cell transcriptome and CITE-seq analyses found reduced frequencies of plasmablasts, TCF7+CD27+GZMK+ T cells and proliferating MKI67-expressing lymphocytes among KTR non-responders. Importantly, the frequency and absolute number of antigen-specific circulating plasmablasts in the whole cohort correlated with the Ig response, a characteristic not reported for other vaccinations. In conclusion, this data indicate that lack of T cell help related to immunosuppression results in impaired germinal center differentiation of B and plasma cell memory. There is an urgent need to improve vaccination protocols in patients after kidney transplantation or on chronic dialysis. One Sentence SummaryKidney transplant recipients and dialysis patients show a markedly diminished humoral response and impaired molecular B cell memory formation upon vaccination with BNT162b2.
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Novel mRNA-based vaccines have been proven powerful tools to combat the global pandemic caused by SARS-CoV2 with BNT162b2 efficiently protecting individuals from COVID-19 across a broad age range. Still, it remains largely unknown how renal insufficiency and immunosuppressive medication affect development of vaccine induced immunity. We therefore comprehensively analyzed humoral and cellular responses in kidney transplant recipients after prime-boost vaccination with BNT162b2. As opposed to all healthy vaccinees and the majority of hemodialysis patients, only 4/39 and 1/39 transplanted individuals showed IgA and IgG seroconversion at day 8{+/-}1 after booster immunization with minor changes until day 23{+/-}5, respectively. Although most transplanted patients mounted spike-specific T helper cell responses, frequencies were significantly reduced compared to controls and dialysis patients, accompanied by a broad impairment in effector cytokine production, memory differentiation and activation-related signatures. Spike-specific CD8+ T cell responses were less abundant than their CD4+ counterparts in healthy controls and hemodialysis patients and almost undetectable in transplant patients. Signs of alloreactivity promoted by BNT162b2 were not documented within the observation period. In summary, our data strongly suggest revised vaccination approaches in immunosuppressed patients, including individual immune monitoring for protection of this vulnerable group at risk to develop severe COVID-19.
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ObjectivePatients with kidney failure have notoriously weak responses to common vaccines. Thus, immunogenicity of novel SARS-CoV-2 vaccines might be impaired in this group. To determine immunogenicity of SARS-CoV-2 vaccination in patients with chronic dialysis, we analyzed the humoral and T-cell response after two doses of mRNA vaccine Tozinameran (BNT162b2 BioNTech/Pfizer). Design, Settings, and ParticipantsThis observational study included 43 patients on dialysis before vaccination with two doses of Tozinameran 21 days apart. Overall, 36 patients completed the observation period. Serum samples were analyzed by SARS-CoV-2 specific antibodies [~]1 and [~]3-4 weeks after the second vaccination. In addition, SARS-CoV-2-specific T-cell responses were assessed at the later time point by an interferon-gamma release assay (IGRA). Outcomes at later timepoints were compared to a group of 44 elderly patients with no dialysis after immunization with Tozinameran. ExposuresBlood drawings during regular laboratory routine assessment right before start of dialysis therapy or at the time of vaccination and at follow-up study visits. Main Outcomes and MeasuresAssessment of immunogenicity after vaccination against SARS-CoV-2 in patients on and without dialysis. ResultsMedian age of patients on chronic dialysis was 74.0 years (IQR 66.0, 82.0). The proportion of males was higher (69.4%) than females. Only 20/36 patients (55.6%, 95%CI: 38.29-71.67) developed SARS-CoV-2-IgG antibodies at first sampling, whereas 32/36 patients (88.9%, 95%CI:73.00-96.38) demonstrated seropositivity at the second sampling. Seroconversion rates and antibody titers were significantly lower compared to a cohort of vaccinees with similar age but no chronic dialysis (>90% seropositivity). SARS-CoV-2-specific T-cell responses 3 weeks after second vaccination were detected in 21/31 vaccinated dialysis patients (67.7%, 95%CI: 48.53-82.68) compared to 42/44 (93.3%, 95%CI: 76.49-98.84) in controls of similar age. Conclusion and RelevancePatients on dialysis demonstrate a delayed, but robust immune response three weeks after the second dose, which indicates effective vaccination of this vulnerable group. However, the lower immunogenicity of Tozinameran in these patients needs further attention to develop potential countermeasures such as an additional booster vaccination.
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Background@#Infantile hemangioma (IH) is one of the most common tumors in infants. IH occurs more commonly in premature and low birth weight infants, but only a few studies have analyzed the risk factors for IH in neonatal intensive care units (NICUs) in Korea. @*Objective@#We investigated the risk factors for IH in patients admitted to the NICU at a single institution. @*Methods@#A single-center retrospective case-control study was conducted in 37 patients with hemangioma and 185 matched-control babies who were admitted to the NICU between 2013 and 2020. Odds ratios (ORs) and multivariate conditional logistic regression models were used to determine the associations between IH and the potential risk factors. @*Results@#Of the 1,206 neonates admitted to the NICU, 37 had IH, and the prevalence was 3.1%. IH was most commonly found on the trunk (33.3%), followed by the head and neck (29.4%). After adjustment, the risk factors found to be significantly associated with IH were female sex (OR=3.0, 95% confidence interval [CI]=1.4∼6.8), extreme preterm (OR=6.9, 95% CI=1.3∼38.0), very low birth weight (OR=11.9, 95% CI=2.9∼49.3), low 1-minute Apgar scores of ＜7 (OR=2.3, 95% CI=1.1∼4.9), and multiple gestation (OR=5.0, 95% CI=1.7∼14.9). @*Conclusion@#This matched case–control study revealed that risk factors such as female sex, extremely preterm birth, very low birth weight, low 1-minute Apgar score, and multiple gestations may affect the occurrence of IH. Therefore, if these risk factors are present, they need to be actively managed at an early stage through close physical examination to prevent complications.
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Background@#Infantile hemangioma (IH) is one of the most common tumors in infants. IH occurs more commonly in premature and low birth weight infants, but only a few studies have analyzed the risk factors for IH in neonatal intensive care units (NICUs) in Korea. @*Objective@#We investigated the risk factors for IH in patients admitted to the NICU at a single institution. @*Methods@#A single-center retrospective case-control study was conducted in 37 patients with hemangioma and 185 matched-control babies who were admitted to the NICU between 2013 and 2020. Odds ratios (ORs) and multivariate conditional logistic regression models were used to determine the associations between IH and the potential risk factors. @*Results@#Of the 1,206 neonates admitted to the NICU, 37 had IH, and the prevalence was 3.1%. IH was most commonly found on the trunk (33.3%), followed by the head and neck (29.4%). After adjustment, the risk factors found to be significantly associated with IH were female sex (OR=3.0, 95% confidence interval [CI]=1.4∼6.8), extreme preterm (OR=6.9, 95% CI=1.3∼38.0), very low birth weight (OR=11.9, 95% CI=2.9∼49.3), low 1-minute Apgar scores of ＜7 (OR=2.3, 95% CI=1.1∼4.9), and multiple gestation (OR=5.0, 95% CI=1.7∼14.9). @*Conclusion@#This matched case–control study revealed that risk factors such as female sex, extremely preterm birth, very low birth weight, low 1-minute Apgar score, and multiple gestations may affect the occurrence of IH. Therefore, if these risk factors are present, they need to be actively managed at an early stage through close physical examination to prevent complications.
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Background@#Dental caries is the most prevalent chronic infectious oral disease of multifactorial etiology. Increased risk of dental caries development in patients with asthma and allergic rhinitis has been frequently reported. In contrast, only a few studies on dental caries in patients with atopic dermatitis (AD) have been reported. @*Objective@#We investigated the association between AD and dental caries development in an adult population in the Republic of Korea. @*Methods@#A total of 21,606 adults who participated in the Korean National Health and Nutrition Examination Survey, a nationwide, population-based, cross-sectional survey between 2010 and 2015, were included in the study. Multiple logistic regression analyses with confounder adjustment suggested odds ratios (ORs) to identify the possible association between AD and decayed, missing, filled teeth (DMFT) experience compared to non-AD participants. Multiple Poisson regression analyses estimated the mean ratio of the DMFT index according to the presence of AD. @*Results@#After adjusting for various confounding factors, the prevalence of DMFT was significantly associated with AD (OR, 1.58; 95% confidence interval (CI), 1.08∼2.29; p=0.017). In addition, the mean value of the DMFT index was significantly different between the AD and non-AD groups (mean ratio, 1.07; 95% CI, 1.00∼1.14; p= 0.046). @*Conclusion@#AD was significantly associated with the development of dental caries. Dermatologists should be aware of the dental manifestations of AD patients and recommend regular dental check-ups for the early detection of caries.
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Background@#Chronic actinic dermatitis is a rare, acquired, persistent eczematous eruption of photo-distributed areas.There are limited data available on the clinical characteristics of Korean patients diagnosed with chronic actinic dermatitis. @*Objective@#To evaluate the clinical features and prognosis of chronic actinic dermatitis patients in Korea. @*Methods@#Sixty-two Korean patients diagnosed with chronic actinic dermatitis through clinical findings, phototesting, and skin biopsy from six hospitals were included in this study, and their clinical characteristics were evaluated. @*Results@#Among the 62 patients, 51 were men, and the mean age at diagnosis was 60.3±12.8 years. Phototesting was performed for 27 patients, with results available for 18 patients. Patch tests were performed for only 4.8% of the patients. Skin pathology tests were performed for 47 patients and showed the following: spongiosis, acanthosis, actinic elastosis, and pseudo-lymphomatous change. Twelve patients were clinically diagnosed without using diagnostic tools such as phototesting, patch testing, and skin biopsy. The most commonly used systemic treatments were antihistamine, cyclosporine, steroid, and azathioprine. Although avoiding ultraviolet irradiation and outdoor activities are critical, only 22.6% of patients used sunscreen. @*Conclusion@#Although phototesting is highly recommended for diagnosing chronic actinic dermatitis, phototesting was performed for less than half of the patients to diagnose chronic actinic dermatitis. Patch tests and photopatch tests are also recommended to disclose a causative agent.
ABSTRACT
Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.
ABSTRACT
Background@#Chronic actinic dermatitis is a rare, acquired, persistent eczematous eruption of photo-distributed areas.There are limited data available on the clinical characteristics of Korean patients diagnosed with chronic actinic dermatitis. @*Objective@#To evaluate the clinical features and prognosis of chronic actinic dermatitis patients in Korea. @*Methods@#Sixty-two Korean patients diagnosed with chronic actinic dermatitis through clinical findings, phototesting, and skin biopsy from six hospitals were included in this study, and their clinical characteristics were evaluated. @*Results@#Among the 62 patients, 51 were men, and the mean age at diagnosis was 60.3±12.8 years. Phototesting was performed for 27 patients, with results available for 18 patients. Patch tests were performed for only 4.8% of the patients. Skin pathology tests were performed for 47 patients and showed the following: spongiosis, acanthosis, actinic elastosis, and pseudo-lymphomatous change. Twelve patients were clinically diagnosed without using diagnostic tools such as phototesting, patch testing, and skin biopsy. The most commonly used systemic treatments were antihistamine, cyclosporine, steroid, and azathioprine. Although avoiding ultraviolet irradiation and outdoor activities are critical, only 22.6% of patients used sunscreen. @*Conclusion@#Although phototesting is highly recommended for diagnosing chronic actinic dermatitis, phototesting was performed for less than half of the patients to diagnose chronic actinic dermatitis. Patch tests and photopatch tests are also recommended to disclose a causative agent.
ABSTRACT
Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.
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BACKGROUND: Recently, the number of nationwide medical researches on psoriasis using the National Health Insurance Service database has been on the rise. However, identification of psoriasis using diagnostic codes alone can lead to misclassification. Accuracy of the diagnostic codes and their concordance with medical records should be validated first to identify psoriasis patients correctly.OBJECTIVE: To validate the diagnostic codes of psoriasis (International Classification of Diseases, 10th Revision L40) and to find the algorithm for the identification of psoriasis.METHODS: We collected medical records of patients who received their first diagnostic codes of psoriasis during 5 years from five hospitals. Fifteen percent of psoriasis patients were randomly selected from each hospital. We performed a validation by reviewing medical records and compared 5 algorithms to identify the best algorithm.RESULTS: Total of 538 cases were reviewed and classified as psoriasis (n=368), not psoriasis (n=159), and questionable (n=11). The most accurate algorithm was including patients with ≥1 visits with psoriasis as primary diagnostic codes and prescription of vitamin D derivatives. Its positive predictive value was 96.5% (95% confidence interval [CI], 93.9%~98.1%), which was significantly higher than those of the algorithm, including patients with ≥1 visits with psoriasis as primary diagnostic codes or including ≥1 visits with diagnostic codes of psoriasis (primary or additional) (91.0% and 69.8%). Sensitivity was 90.8% (95% CI, 87.2%~93.4%) and specificity was 92.5% (95% CI, 86.9%~95.9%).CONCLUSION: Our study demonstrates a validated algorithm to identify psoriasis, which will be useful for the nationwide population-based study of psoriasis in Korea.
Subject(s)
Humans , Classification , Electronic Health Records , International Classification of Diseases , Korea , Medical Records , National Health Programs , Prescriptions , Psoriasis , Sensitivity and Specificity , Vitamin DABSTRACT
Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by typical cutaneous manifestation and inflammation of the skeletal muscles. However, this progressive symmetric proximal muscle weakness may be minimal or absent in clinically amyopathic DM (CADM). Importantly, DM has been associated with malignancy, which is related to poor prognosis. Therefore, every newly diagnosed patient with DM should undergo thorough screening investigations for hidden internal malignancy. We report a case of CADM, with severe intractable itching, which was finally diagnosed as paraneoplastic dermatomyositis associated with gastric cancer in a 77-year-old woman. The patient had typical cutaneous features of DM and mild elevation of muscle enzymes without muscle weakness.
Subject(s)
Aged , Female , Humans , Dermatomyositis , Inflammation , Mass Screening , Muscle Weakness , Muscle, Skeletal , Myositis , Paraneoplastic Syndromes , Prognosis , Pruritus , Stomach NeoplasmsABSTRACT
Cheilitis granulomatosa (CG) is a subset of orofacial granulomatosis (OFG) and considered to be a monosymptomatic form of Melkersson-Rosenthal syndrome (MRS), which is characterized by the triad of chronic lip swelling, facial paralysis, and fissured tongue. The labial swelling is thought to be associated with an orofacial swelling, which affects the chin, cheeks, and oral mucosa. Histologically, it is distinguished by noncaseating granulomas consisting of lymphohistiocytes and giant cells. Although systemic steroids with or without intralesional triamcinolone injections are the mainstay of treatment, and various agents have been proposed for this rare disease, no successful treatment modality has been reported in the literature yet. Herein, we present our experience with three different CG cases, which showed a varied level of positive response to the combination therapy.
