Disseminated Granuloma Annulare Research Articles

Successful Treatment of Disseminated Granuloma Annulare with Upadacitinib.

Disseminated granuloma annulare (DGA) is an inflammatory skin disorder characterized by more than 10 erythematous, raised, ring-shaped plaques. Its treatment remains challenging, with conventional therapies showing variable efficacy. We report the case of a woman in her 50s with a 2-year history of DGA refractory to multiple treatments. Given the recent evidence of the role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in the granuloma annulare pathophysiology, treatment with upadacitinib 30mg per day was started with rapid effectiveness and good tolerance. This case underscores the potential of JAK inhibitors as promising therapeutic options for recalcitrant granuloma annulare.

Successful treatment of disseminated granuloma annulare with adalimumab

Granuloma annulare (GA) is a chronic inflammatory necrobiotic granulomatous skin disease, which is based on a delayed hypersensitivity reaction caused by the production of interferon- (IFN-) by tissue macrophages and th1-limocytes, tumor necrosis factor- (TNF-) and matrix metalloproteinases (MMP), which leads to the degradation of connective tissue.
 The most frequent form of GA if localized which is characterized clinically by grouped papules and plaques of red or pink color on the extremities. although disseminated variants of disease occur in 15% of all cases of ag. in contrast to the practically asymptomatic course of the localized form, typical signs of disseminated form are intensive sense of itching, the presence of at least ten foci of skin lesions, recurrent and resistance to treatment course.
 A 53-year-old female patient with a long-term recurrent course of annular granuloma after a weak clinical response to therapy with pentoxifilin, methotrexate and azathioprine turned to the dermatology department of the university hospital. In light of the lack of satisfactory treatment options anti-cytokine therapy with adalimumab was recommended at a daily dosage of 80 mg, once a week, for 2 weeks, then 1 time every two weeks for 1.5 months. Already on the 5th day after receiving the first injection, the patient reported that the feeling of itching disappeared. By the end of the second week of the induction phase of biotherapy, it became obvious that new rashes did not appear, and the old elements of the skin rash had significantly flattened, turned pale and decreased in volume. After the second week of consolidated therapy, the dermatologist confirmed the convalescence.

Dimethyl Fumarate Used as an Effective Treatment for Granuloma Annulare Disseminatum: An Immunohistochemical Case Study.

This investigation demonstrates the use of dimethyl fumarate (DMF) for the treatment of disseminated granuloma annulare (GAD), a rare and chronic inflammatory skin disease. In this case, progressive GAD was treated with DMF, resulting in significant improvement of skin lesions within 5 weeks and complete healing within 7 months. Clinical response was associated with a reduction in inflammatory cells, including both T cell subsets (CD4+ > CD8+), CD183+/CXCR3+ cells, Langerhans cells (CD1a+), myeloid DCs, M1- and M2-like macrophages and the activation marker HLA-DR in immunohistochemical analysis. These findings support the use of DMF as a promising treatment option for this rare skin condition.

Effects of canary seed on two patients with disseminated granuloma annulare.

Treatment of disseminated granuloma annulare (GA) can be challenging and there is no gold standard for treatment. We observed two cases of generalized GA that were treated successfully with canary seed milk despite being resistant to other treatments. Canary seed milk has antioxidant (contains vitamin E), anti-diabetic (DPP-4 inhibition), and anti-hypertensive (ACE inhibition) properties. Therefore, dermatologists can consider canary seed milk, also known as alpiste milk, as a sole or supplemental treatment for patients with GA with or without comorbidities such as diabetes and hypertension, who prefer alternative therapy or failed other treatments.

Non-FDA-Approved Uses of Apremilast in Dermatology: A Review of Current Available literature

Introduction: Apremilast, an oral phosphodiesterase-4 inhibitor, decreases the production of pro-inflammatory cytokines including tumour necrosis factor-α, interleukin-12/23, IL-12, IL-2, and interferon-γ; while upregulating the anti-inflammatory cytokine IL-10. Its pan-immunomodulatory nature has led to its use in managing various immune-mediated dermatoses for non-FDA-approved indications. Objectives: To review and analyze the use of Apremilast in Non-FDA-approved indications in current available literature. Materials and methods: PubMed, EMBASE, SCOPUS, and Google scholar databases were searched with the parameters “Apremilast”, “Apremilast NOT Psoriasis*”, “Apremilast NOT Behçet’s*”, and “Apremilast NOT arthritis*”. A total of 45 relevant articles were chosen for review. Results: We found 22 indications in dermatology where apremilast has been used without FDA approval. The best evidence was for treatment in Atopic Dermatitis, Alopecia Areata, and Hidradenitis Suppurativa, with randomized controlled trials. Prospective open-label trials were found for Cutaneous Sarcoidosis, Lichen Planus, Rosacea, and Vitiligo. Individual case series and reports were found for Acrodermatitis Continua of Hallopeau, Dermatomyositis, Disseminated Granuloma Annulare, Erythema Nodosum Leprosum, Morphea, Pityriasis Rubra Pilaris, Hailey-Hailey Disease, Recurrent Erythema Multiforme, and Folliculitis Decalvans, Prurigo Nodularis, Perforating Dermatoses, Chronic Actinic Dermatitis, and Hand Eczema, and Epidermolysis Bullosa Simplex-Generalised Severe Type. Apremilast has shown varied efficacy despite a better safety profile and tolerability over a long duration compared to conventional immunosuppressant drugs and placebo. Conclusion: Apremilast has been used for varied non-FDA-approved indications in dermatology with variable efficacy. Better controlled, randomized studies with adequate sample size and drug comparisons are needed for better analyses.

34266 Is generalized granuloma annulare truly associated with diabetes mellitus, hyperlipidemia, thyroid disorders, and malignancy? A systematic review

Objective: Generalized granuloma annulare (GGA) is a rare subtype of granuloma annulare (GA) characterized by its benign, yet chronic recurrent course. Several studies have debated GGA’s association with underlying systemic disease such as diabetes mellitus (DM), dyslipidemia (DLD), malignancy, and thyroid disorders (TD). Our objective was to evaluate the association between GGA and systemic diseases. Methods: The databases PubMed, Embase, and Cochrane Library were searched on June 15, 2021, for “generalized or disseminated granuloma annulare.” Results were reported using the Preferred Reporting Systems for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Results: A total of 579 studies were screened for inclusion, yielding 194 studies with 934 patients. The mean age was 51.2 years, and 68.3% of patients were female.The 3 most common associated systemic conditions were DLD (14.6%, n = 136/934), DM (14.5%, n = 135/934), and TD (9.1%, n = 85/934). A total of 93 malignancies (10.0%, n = 93/934) were reported, 69 being non-hematologic malignancies. In total, 35.5% (n = 33/93) of patients had paraneoplastic GGA. Conclusion: Our evidence-based review showed much lower prevalence of DLD, DM, and TD than previous studies. Moreover, only 15 patients experienced resolution of GGA with appropriate management of these comorbidities. Therefore, only a small percentage of patients seem to have a true association of GGA with systemic disease. However, our findings revealed paraneoplastic GGA in 35.5% of patients with underlying malignancy. Therefore, we advocate that it may be beneficial to update age-appropriate cancer screening in individuals with refractory or severe GGA, and history or signs of underlying malignancy.

Eruptive Xanthomas

A 21-year-old woman with a history of poorly controlled diabetes mellitus presented with a 5-week history of an itchy rash. She reported a recent hospitalization for pancreatitis and a family history of paternal hypertriglyceridemia. Examination revealed numerous pink-to-yellow dome–shaped papules on her back, buttocks, bilateral legs, and arms, accentuated on extensor surfaces (Figures 1 and 2). Although eruptive xanthomas were favored clinically, the differential diagnosis also included multicentric reticulohistiocytosis, disseminated granuloma annulare, and sarcoidosis. Histopathology confirmed extracellular lipid along with intradermal foamy histiocytes (Supplemental Figures 1 and 2, available online at http://www.mayoclinicproceedings.org). Laboratory findings revealed a triglyceride level of 3130 mg/dL (to convert to mmol/L, multiply by 0.0259). On the basis of clinical, histopathological, and laboratory findings, the patient was diagnosed with eruptive xanthomas.Figure 2Clinical image of multiple yellowish papules on the forearm.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Hypertriglyceridemia can be inherited through lipoprotein lipase deficiency or familial hypolipoproteinemia or because of secondary causes such as diabetes mellitus, obesity, alcohol, or estrogen supplementation.1Yuan G. Al-Shali K.Z. Hegele R.A. Hypertriglyceridemia: its etiology, effects and treatment.CMAJ. 2007; 176: 1113-1120Crossref PubMed Scopus (389) Google Scholar Cutaneous xanthomas result when lipids deposit in the dermis within macrophages, known as foam cells, and in the extracellular matrix. They can be divided into eruptive, tuberous, tendon, verruciform, and planar xanthomas. Eruptive xanthomas are associated with elevated serum chylomicron levels and thus hypertriglyceridemia, often exceeding 3000 mg/dL.2Durrington P. Dyslipidaemia.Lancet. 2003; 362: 717-731Abstract Full Text Full Text PDF PubMed Scopus (317) Google Scholar The accumulation of lipid presents as pruritic yellow papules, most commonly on the buttocks and extensor surfaces of extremities. Diagnosis can be confirmed by histopathology with a histiocytic perivascular infiltrate, extracellular lipid, and lipidized macrophages.3Merola J.F. Mengden S.J. Soldano A. Rosenman K. Eruptive xanthomas.Dermatol Online J. 2008; 14: 10Crossref PubMed Google Scholar Failure to diagnose and treat hyperlipidemia leads to an increased risk of atherosclerosis, cardiovascular disease, and pancreatitis.4Sarwar N. Danesh J. Eiriksdottir G. et al.Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies.Circulation. 2007; 115: 450-458Crossref PubMed Scopus (1079) Google Scholar,5Roga G. Jithendriya M. Eruptive xanthoma: warning sign of systemic disease.Cleve Clin J Med. 2016; 83: 715-716Crossref PubMed Scopus (6) Google Scholar Along with lifestyle modification, treatment of hypertriglyceridemia with fibrates or niacin results in regression of xanthomas while aiming to prevent systemic complications.5Roga G. Jithendriya M. Eruptive xanthoma: warning sign of systemic disease.Cleve Clin J Med. 2016; 83: 715-716Crossref PubMed Scopus (6) Google Scholar A 21-year-old woman with a history of poorly controlled diabetes mellitus presented with a 5-week history of an itchy rash. She reported a recent hospitalization for pancreatitis and a family history of paternal hypertriglyceridemia. Examination revealed numerous pink-to-yellow dome–shaped papules on her back, buttocks, bilateral legs, and arms, accentuated on extensor surfaces (Figures 1 and 2). Although eruptive xanthomas were favored clinically, the differential diagnosis also included multicentric reticulohistiocytosis, disseminated granuloma annulare, and sarcoidosis. Histopathology confirmed extracellular lipid along with intradermal foamy histiocytes (Supplemental Figures 1 and 2, available online at http://www.mayoclinicproceedings.org). Laboratory findings revealed a triglyceride level of 3130 mg/dL (to convert to mmol/L, multiply by 0.0259). On the basis of clinical, histopathological, and laboratory findings, the patient was diagnosed with eruptive xanthomas. Hypertriglyceridemia can be inherited through lipoprotein lipase deficiency or familial hypolipoproteinemia or because of secondary causes such as diabetes mellitus, obesity, alcohol, or estrogen supplementation.1Yuan G. Al-Shali K.Z. Hegele R.A. Hypertriglyceridemia: its etiology, effects and treatment.CMAJ. 2007; 176: 1113-1120Crossref PubMed Scopus (389) Google Scholar Cutaneous xanthomas result when lipids deposit in the dermis within macrophages, known as foam cells, and in the extracellular matrix. They can be divided into eruptive, tuberous, tendon, verruciform, and planar xanthomas. Eruptive xanthomas are associated with elevated serum chylomicron levels and thus hypertriglyceridemia, often exceeding 3000 mg/dL.2Durrington P. Dyslipidaemia.Lancet. 2003; 362: 717-731Abstract Full Text Full Text PDF PubMed Scopus (317) Google Scholar The accumulation of lipid presents as pruritic yellow papules, most commonly on the buttocks and extensor surfaces of extremities. Diagnosis can be confirmed by histopathology with a histiocytic perivascular infiltrate, extracellular lipid, and lipidized macrophages.3Merola J.F. Mengden S.J. Soldano A. Rosenman K. Eruptive xanthomas.Dermatol Online J. 2008; 14: 10Crossref PubMed Google Scholar Failure to diagnose and treat hyperlipidemia leads to an increased risk of atherosclerosis, cardiovascular disease, and pancreatitis.4Sarwar N. Danesh J. Eiriksdottir G. et al.Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies.Circulation. 2007; 115: 450-458Crossref PubMed Scopus (1079) Google Scholar,5Roga G. Jithendriya M. Eruptive xanthoma: warning sign of systemic disease.Cleve Clin J Med. 2016; 83: 715-716Crossref PubMed Scopus (6) Google Scholar Along with lifestyle modification, treatment of hypertriglyceridemia with fibrates or niacin results in regression of xanthomas while aiming to prevent systemic complications.5Roga G. Jithendriya M. Eruptive xanthoma: warning sign of systemic disease.Cleve Clin J Med. 2016; 83: 715-716Crossref PubMed Scopus (6) Google Scholar We thank Cacey Peters, MD, from Department of Dermatology, the University of Tennessee Health Science Center, for providing the supplemental images. Supplemental Online MaterialSupplemental Figure 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Oral dapsone for the treatment of generalized granuloma annulare: A retrospective case series

To the Editor: Granuloma annulare is a non-infectious granulomatous dermatosis. Although its etiology is unknown, some conditions have been reported in increased frequencies in patients with granuloma annulare compared with the general population, including thyroid disease, diabetes mellitus, dyslipidemia, and viral infections.1Wang J. Khachemoune A. Granuloma annulare: a focused review of therapeutic options.Am J Clin Dermatol. 2018; 19: 333-344Crossref PubMed Scopus (37) Google Scholar While localized disease tends to spontaneously resolve, generalized granuloma annulare (GGA) cases may persist for decades, and the treatment data are sparse.1Wang J. Khachemoune A. Granuloma annulare: a focused review of therapeutic options.Am J Clin Dermatol. 2018; 19: 333-344Crossref PubMed Scopus (37) Google Scholar Phototherapy and antimalarials are the first-line treatment for GGA, although retinoids, biologics, and small molecule immunosuppressants can also be used.1Wang J. Khachemoune A. Granuloma annulare: a focused review of therapeutic options.Am J Clin Dermatol. 2018; 19: 333-344Crossref PubMed Scopus (37) Google Scholar Dapsone may be viable; however, evidence is limited to studies comprising ≤10 patients.2Czarnecki D.B. Gin D. The response of generalized granuloma annulare to dapsone.Acta Derm Venereol. 1986; 66: 82-84PubMed Google Scholar, 3Steiner A. Pehamberger H. Wolff K. Sulfone treatment of granuloma annulare.J Am Acad Dermatol. 1985; 13: 1004-1008Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 4Martín-Sáez E. Fernández-Guarino M. Carrillo-Gijón R. Muñoz-Zato E. Jaén-Olasolo P. Efficacy of dapsone in disseminated granuloma annulare: a case report and review of the literature. Article in Spanish.Actas Dermosifiliogr. 2008; 99: 64-68Crossref PubMed Scopus (19) Google Scholar Here, we evaluate the safety and efficacy of dapsone with a retrospective case series of 26 patients.Institutional review board approval was obtained to review the medical records of patients from a single institution who received oral dapsone for GGA between 2010 and 2020. Patients without pretreatment biopsy and patients lost to follow-up were excluded. Outcomes were categorized as: complete clearance, partial response (fewer, flattened, or faded lesions), or no improvement.Twenty-six patients—primarily Caucasian (100%) women (96%) with a mean age of 64 years—met the inclusion criteria (Table I). Lesions were most commonly plaque-type (24/26; 92%), and involved the lower extremities (23/26; 88%), upper extremities (21/26; 81%), trunk (17/26; 65%), and neck (2/26; 8%); 12 (46%) patients reported pruritus, 4 (15%) patients reported burning pain, and 13 (50%) patients were asymptomatic. The patients had mean disease duration of 5.6 years before initiating dapsone at a median daily dose of 100 mg (25-200 mg) for a mean duration of 9.8 months. Fourteen of 26 (54%) patients improved, and initial responses were observed within a mean of 2.3 months. However, the results were not consistently sustained, and 8 (57%) responders experienced flares following discontinuation. The patients who improved remained on dapsone for longer durations compared with those who did not improve (mean 16.0 vs 2.6 months), and perceived lack of efficacy was the most common discontinuation reason in non-responders (8/12; 67%).Table IPresentation characteristics of 26 patients with generalized granuloma annulare treated with dapsoneAge, y/sex/raceComorbid conditionsGeneralized granuloma annulare disease sitesLesion morphologyPre-dapsone therapiesDapsone maximum daily dose, mg (duration, mo)Adjunctive medicationsOutcome (initial response, mo)Adverse effectsCessation reason74/F/WHypothyroidism, VZVLE, trunkPlaques, patchesClobetasol, topical tacrolimus50 (39)NoneComplete clearance (1)∗Experienced flares after initial response to dapsone.NoneDeath (unrelated)62/F/WHypothyroidism, T2DM, VZVUE, LE, trunkPlaquesNone150 (15)NonePR (0.75)Myelosuppression (3.3 WBC, 11.9 Hg, 137 PLT)Myelosuppression88/F/WNoneUE, LEPlaquesHCQ50 (17)NonePR (1)Myelosuppression (4.6 WBC, 10.5 Hg, 105 PLT)Myelosuppression58/F/WNoneUE, LE, trunkPlaquesColchicine, fluocinonide, MTX, phototherapy, topical tacrolimus100 (13)Clobetasol, topical tacrolimusPR (1)Myelosuppression (4.7 WBC, 10.7 Hg)Myelosuppression76/F/WDLP, hypothyroidismUE, LEPlaques, papulesClobetasol100 (1)PhototherapyPR (1)∗Experienced flares after initial response to dapsone.NauseaNausea59/F/WNoneUE, LE, trunkPlaques, papulesNone100 (10)NonePR (1)NoneUnknown66/F/WHypothyroidismUEPapulesNone150 (39)Clobetasol, pentoxifylline, rifampin/ofloxacin/minocyclinePR (1.5)NoneBenefit plateau66/F/WNoneUEPlaquesMTX, pentoxifylline, phototherapy, prednisone, TCSs150 (13)TACPR (2)∗Experienced flares after initial response to dapsone.UTIUTI44/F/WNoneUE, LEPlaquesNone50 (2)ColchicinePR (2)∗Experienced flares after initial response to dapsone.NoneN/A60/F/WHerpes simplex virusUE, LE, trunkPlaquesNone100 (80)NonePR (3)Myelosuppression (Hg 12.1)Myelosuppression50/F/WT2DM, thyroid nodulesUE, LEPlaquesBetamethasone50 (3)BetamethasonePR (3)∗Experienced flares after initial response to dapsone.Myelosuppression (4.3 WBC, 12.2 Hg, 119 PLT)Myelosuppression51/F/WDLP, hypothyroidism, VZVUE, trunkPlaquesHCQ150 (3)NonePR (3)∗Experienced flares after initial response to dapsone.NoneUnknown63/F/WDLP, hypothyroidism, T2DMUE, LE, trunkPlaquesHCQ, ILK, isotretinoin, MTX, phototherapy75 (22)TACPR (4)∗Experienced flares after initial response to dapsone.NoneBenefit plateau49/F/WNoneUE, LE, trunk, neckPlaques, patchesIsotretinoin, MTX, prednisone, rifampin/ofloxacin/minocycline, TCSs200 (39)PhototherapyPR (8)∗Experienced flares after initial response to dapsone.NoneN/A78/F/WDLP, hypothyroidism, T2DM, VZVLEPlaques, papulesHCQ, TAC100 (1)NoneNIMyelosuppression (4.4 WBC, 11.5 Hg)Myelosuppression80/F/WDLP, T2DMUE, LE, trunkPlaques, papulesFluocinonide50 (1)NoneNIMyelosuppression (10.0 Hg)Myelosuppression61/F/WHypothyroidismUE, LEPlaques, patchesNone150 (1)NoneNINoneLack of efficacy53/F/WNoneUE, LE, trunkPlaquesHalobetasol100 (3)NoneNIDyspnea on exertionLack of efficacy67/M/WT2DMUE, LE, trunkPlaquesHCQ, ILK, phototherapy, TCSs100 (6)NoneNINoneLack of efficacy66/F/WVZVLE, trunkPlaquesTCSs50 (4)NoneNINoneLack of efficacy66/F/WDLP, hypothyroidismUE, LE, trunkPlaquesMTX, TCSs50 (2)NoneNINausea, headache, chills, myalgiasLack of efficacy71/F/WNoneLE, trunkPlaquesAzathioprine, ILK, prednisone, topical pimecrolimus150 (3)NoneNINoneLack of efficacy64/F/WDLP, T2DMLEPlaquesClobetasol, HCQ, pentoxifylline, rifampin/ofloxacin/minocycline25 (0.5)NoneNIUTIUTI55/F/WDLP, hypothyroidism, T2DMUE, LE, trunk, neckPlaques, papulesHCQ, ILK, TCSs25 (6)BetamethasoneNINoneLack of efficacy75/F/WDLPUE, LE, trunkPapules, patchesTCSs100 (0.5)NoneNIMyelosuppression (10.7 Hg)Myelosuppression56/F/WDLPUE, LE, trunkPlaquesAcitretin, prednisone100 (3)NoneNINoneN/ADLP, Dyslipidemia, F, female; HCQ, hydroxychloroquine; Hg, hemoglobin level, g/dL; ILK, intralesional triamcinolone; LE, lower extremities; M, male; MTX, methotrexate; N/A, not applicable; NI, no improvement; PLT, platelet count, ×109/L; PR, partial response; TAC, topical triamcinolone; T2DM, type 2 diabetes mellitus; TCSs, unspecified topical corticosteroids; UE, upper extremities; UTI, urinary tract infection; W, Caucasian; WBC, white blood cell count, ×109/L; VZV, Varicella zoster virus.∗ Experienced flares after initial response to dapsone. Open table in a new tab Seventeen of 26 (65%) patients underwent dapsone monotherapy, including 6 of 13 (46%) responders. The most common concomitant medications in those who improved with dapsone were topical corticosteroids: betamethasone (2/14; 14%), clobetasol (2/14; 14%), and triamcinolone (2/14; 14%). Several agents were attempted before dapsone treatment but failed to yield results or caused unbearable side effects (Table I). Although dapsone was subjectively well-tolerated (2 patients complained of nausea), nearly 1 in 3 patients (8/26; 31%) experienced subclinical myelosuppression (median 12 months after initiating dapsone), which warranted treatment cessation. Dapsone is associated with a variety of local and systemic adverse effects that may preclude its viability.5Ghaoui N. Hanna E. Abbas O. Kibbi A.G. Kurban M. Update on the use of dapsone in dermatology.Int J Dermatol. 2020; 59: 787-795Crossref PubMed Scopus (28) Google ScholarThe management of GGA can be challenging. Granulomatous inflammation can be slow to both form and resolve, and the effects of therapy may not be observed for 3-6 months.1Wang J. Khachemoune A. Granuloma annulare: a focused review of therapeutic options.Am J Clin Dermatol. 2018; 19: 333-344Crossref PubMed Scopus (37) Google Scholar The evidence to support dapsone for GGA remains debatable as clinical responses may not be durable nor consistently achieved, and the patients may experience treatment-limiting side effects. However, these results contribute to the limited pool of data for a condition which has no definitive treatment option. To the Editor: Granuloma annulare is a non-infectious granulomatous dermatosis. Although its etiology is unknown, some conditions have been reported in increased frequencies in patients with granuloma annulare compared with the general population, including thyroid disease, diabetes mellitus, dyslipidemia, and viral infections.1Wang J. Khachemoune A. Granuloma annulare: a focused review of therapeutic options.Am J Clin Dermatol. 2018; 19: 333-344Crossref PubMed Scopus (37) Google Scholar While localized disease tends to spontaneously resolve, generalized granuloma annulare (GGA) cases may persist for decades, and the treatment data are sparse.1Wang J. Khachemoune A. Granuloma annulare: a focused review of therapeutic options.Am J Clin Dermatol. 2018; 19: 333-344Crossref PubMed Scopus (37) Google Scholar Phototherapy and antimalarials are the first-line treatment for GGA, although retinoids, biologics, and small molecule immunosuppressants can also be used.1Wang J. Khachemoune A. Granuloma annulare: a focused review of therapeutic options.Am J Clin Dermatol. 2018; 19: 333-344Crossref PubMed Scopus (37) Google Scholar Dapsone may be viable; however, evidence is limited to studies comprising ≤10 patients.2Czarnecki D.B. Gin D. The response of generalized granuloma annulare to dapsone.Acta Derm Venereol. 1986; 66: 82-84PubMed Google Scholar, 3Steiner A. Pehamberger H. Wolff K. Sulfone treatment of granuloma annulare.J Am Acad Dermatol. 1985; 13: 1004-1008Abstract Full Text PDF PubMed Scopus (58) Google Scholar, 4Martín-Sáez E. Fernández-Guarino M. Carrillo-Gijón R. Muñoz-Zato E. Jaén-Olasolo P. Efficacy of dapsone in disseminated granuloma annulare: a case report and review of the literature. Article in Spanish.Actas Dermosifiliogr. 2008; 99: 64-68Crossref PubMed Scopus (19) Google Scholar Here, we evaluate the safety and efficacy of dapsone with a retrospective case series of 26 patients. Institutional review board approval was obtained to review the medical records of patients from a single institution who received oral dapsone for GGA between 2010 and 2020. Patients without pretreatment biopsy and patients lost to follow-up were excluded. Outcomes were categorized as: complete clearance, partial response (fewer, flattened, or faded lesions), or no improvement. Twenty-six patients—primarily Caucasian (100%) women (96%) with a mean age of 64 years—met the inclusion criteria (Table I). Lesions were most commonly plaque-type (24/26; 92%), and involved the lower extremities (23/26; 88%), upper extremities (21/26; 81%), trunk (17/26; 65%), and neck (2/26; 8%); 12 (46%) patients reported pruritus, 4 (15%) patients reported burning pain, and 13 (50%) patients were asymptomatic. The patients had mean disease duration of 5.6 years before initiating dapsone at a median daily dose of 100 mg (25-200 mg) for a mean duration of 9.8 months. Fourteen of 26 (54%) patients improved, and initial responses were observed within a mean of 2.3 months. However, the results were not consistently sustained, and 8 (57%) responders experienced flares following discontinuation. The patients who improved remained on dapsone for longer durations compared with those who did not improve (mean 16.0 vs 2.6 months), and perceived lack of efficacy was the most common discontinuation reason in non-responders (8/12; 67%). DLP, Dyslipidemia, F, female; HCQ, hydroxychloroquine; Hg, hemoglobin level, g/dL; ILK, intralesional triamcinolone; LE, lower extremities; M, male; MTX, methotrexate; N/A, not applicable; NI, no improvement; PLT, platelet count, ×109/L; PR, partial response; TAC, topical triamcinolone; T2DM, type 2 diabetes mellitus; TCSs, unspecified topical corticosteroids; UE, upper extremities; UTI, urinary tract infection; W, Caucasian; WBC, white blood cell count, ×109/L; VZV, Varicella zoster virus. Seventeen of 26 (65%) patients underwent dapsone monotherapy, including 6 of 13 (46%) responders. The most common concomitant medications in those who improved with dapsone were topical corticosteroids: betamethasone (2/14; 14%), clobetasol (2/14; 14%), and triamcinolone (2/14; 14%). Several agents were attempted before dapsone treatment but failed to yield results or caused unbearable side effects (Table I). Although dapsone was subjectively well-tolerated (2 patients complained of nausea), nearly 1 in 3 patients (8/26; 31%) experienced subclinical myelosuppression (median 12 months after initiating dapsone), which warranted treatment cessation. Dapsone is associated with a variety of local and systemic adverse effects that may preclude its viability.5Ghaoui N. Hanna E. Abbas O. Kibbi A.G. Kurban M. Update on the use of dapsone in dermatology.Int J Dermatol. 2020; 59: 787-795Crossref PubMed Scopus (28) Google Scholar The management of GGA can be challenging. Granulomatous inflammation can be slow to both form and resolve, and the effects of therapy may not be observed for 3-6 months.1Wang J. Khachemoune A. Granuloma annulare: a focused review of therapeutic options.Am J Clin Dermatol. 2018; 19: 333-344Crossref PubMed Scopus (37) Google Scholar The evidence to support dapsone for GGA remains debatable as clinical responses may not be durable nor consistently achieved, and the patients may experience treatment-limiting side effects. However, these results contribute to the limited pool of data for a condition which has no definitive treatment option. Dr Feldman has received research, speaking, and/or consulting support from a variety of companies including Galderma , GSK / Stiefel , Almirall , Leo Pharma , Boehringer Ingelheim , Mylan , Celgene , Pfizer , Valeant , Abbvie , Samsung , Janssen , Lilly , Menlo , Merck , Novartis , Regeneron , Sanofi , Novan , Qurient , National Biological Corporation , Caremark , Advance Medical , Sun Pharma , Suncare Research , Informa , UpToDate , and National Psoriasis Foundation and is the founder and majority owner of www.DrScore.com and the founder and part owner of Causa Research, a company dedicated to enhancing patients' adherence to treatment. Authors Hrin, Bashyam, and Huang have no conflicts of interest to declare.

A clinic epidemiological study of cutaneous markers of internal malignancy

<p class="abstract"><strong>Background:</strong> The skin provides important clues to many systemic diseases. Changes in the skin can be a marker for internal malignancies. If any cutaneous disorder associated with malignancy can be recognized early, it paves way to rapid diagnosis and treatment of the underlying malignancy. we made such an attempt to recognize cutaneous disorders in 40 patients suffering with internal malignancies at government general hospital, Guntur attending dermatology and radiology departments.</p><p class="abstract"><strong>Methods:</strong> Patients with internal malignancy having specific features were included in our study. Biopsy was done in every patient. The present study lasted for 21 months i.e., from January 2008 to September 2009.<strong></strong></p><p class="abstract"><strong>Results:</strong> We found that carcinoma cervix was the most common malignancy in females and bronchogenic carcinoma in males associated with cutaneous markers. The markers observed were pruritus, acquired lymphorroids, para neoplastic pemphigus, acquired icthyosis and disseminated granuloma annulare. Cutaneous markers were observed within 6 months from onset of internal malignancies.</p><p class="abstract"><strong>Conclusions:</strong> Recognition of any para-neoplastic skin disorders should raise suspicion for an internal malignancy which helps in rapid diagnosis and treatment of underlying malignancy.</p>

Combination treatment of disseminated granuloma annulare

Purpose. To present the results of the treatment of disseminated form of granuloma annulare with remote long-wave ultraviolet therapy and low level laser therapy.
 Material and methods. Two female patients at the age of 50 and 53 years with complaints of generalised eruptions on the skin of the trunk, upper and lower limbs and a histologically confirmed diagnosis were treated using a combination of remote long-wave ultraviolet therapy and low level laser therapy of infrared spectrum. 16 sessions of remote long-wave ultraviolet therapy and 10 sessions of low level laser therapy were conducted directly on the lesions. Considering the multidirectionality of the mechanisms of action of phototherapy and laser therapy, the procedures were carried out on different days or with many hours long intervals.
 Results. Combined use of the remote long-wave ultraviolet therapy and laser therapy led to a significant improvement by the 21st day of the treatment. No side effects were noticed during the treatment, tolerance of the sessions was good.
 Conclusion. Combined use of the remote long-wave ultraviolet therapy and low level laser therapy of infrared spectrum is effective in treatment of disseminated form of granuloma annulare.

Skuteczne leczenie rozsianej postaci ziarniniaka obrączkowatego z zastosowaniem kremu z imikwimodem 5% u 10-letniej pacjentki

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Nowak M, Barańska-Rybak W, Opalska-Tuszyńska A. Successful treatment of disseminated granuloma annulare in a 10-year-old patient with 5% imiquimod cream. Dermatology Review/Przegląd Dermatologiczny. 2020;107(6):566-568. doi:10.5114/dr.2020.103894. APA Nowak, M., Barańska-Rybak, W., & Opalska-Tuszyńska, A. (2020). Successful treatment of disseminated granuloma annulare in a 10-year-old patient with 5% imiquimod cream. Dermatology Review/Przegląd Dermatologiczny, 107(6), 566-568. https://doi.org/10.5114/dr.2020.103894 Chicago Nowak, Marcela, Wioletta Barańska-Rybak, and Adrianna Opalska-Tuszyńska. 2020. "Successful treatment of disseminated granuloma annulare in a 10-year-old patient with 5% imiquimod cream". Dermatology Review/Przegląd Dermatologiczny 107 (6): 566-568. doi:10.5114/dr.2020.103894. Harvard Nowak, M., Barańska-Rybak, W., and Opalska-Tuszyńska, A. (2020). Successful treatment of disseminated granuloma annulare in a 10-year-old patient with 5% imiquimod cream. Dermatology Review/Przegląd Dermatologiczny, 107(6), pp.566-568. https://doi.org/10.5114/dr.2020.103894 MLA Nowak, Marcela et al. "Successful treatment of disseminated granuloma annulare in a 10-year-old patient with 5% imiquimod cream." Dermatology Review/Przegląd Dermatologiczny, vol. 107, no. 6, 2020, pp. 566-568. doi:10.5114/dr.2020.103894. Vancouver Nowak M, Barańska-Rybak W, Opalska-Tuszyńska A. Successful treatment of disseminated granuloma annulare in a 10-year-old patient with 5% imiquimod cream. Dermatology Review/Przegląd Dermatologiczny. 2020;107(6):566-568. doi:10.5114/dr.2020.103894.

Disszeminált granuloma anulare kezelésének lehetőségei egy eset kapcsán

Disszeminált granuloma anulare kezelésének lehetőségei egy eset kapcsán

The role of biologics in the treatment of chronic granuloma annulare.

Granuloma annulare (GA), a benign inflammatory skin disease, is considered a Th1-type delayed hypersensitivity reaction. Localized GA is likely to resolve spontaneously, whereas disseminated GA (DGA) may persist for decades and can be resistant to treatment. Biologics including TNF-α inhibitors have been proposed and utilized as salvage therapy for GA and other related diseases, interstitial granulomatous dermatitis (IGD), and actinic granuloma (AG). A systematic review was conducted using the combination of search terms "granuloma annulare," "interstitial granulomatous dermatitis," or "actinic granuloma" and either "biologics," "etanercept," "adalimumab," "infliximab," "ustekinumab," "ixekizumab," "secukinumab," "guselkumab," "golimumab," "brodalumab," "tildrakizumab," or "certolizumab" from the years 1970-2017. Review of the literature revealed that 79.3% of the patients with GA, IGD, or AG who had been treated with demonstrated TNF-α inhibitor therapy a clinical response. TNF-α inhibitor therapy has been used to treat chronic GA, IGD, and AG that involved extensive body surface areas. However, the literature is limited to case series lacking control groups. Randomized, controlled trials are required to establish evidence-based treatment of GA and related cutaneous, granulomatous conditions.

Skin lesions in diabetes mellitus: risk factors for development, clinical manifestations, prevention and treatment

The overall prevalence of skin lesions in diabetes mellitus varies from 51.1 to 97 %. More than 30 different dermatoses are described that either precede diabetes or develop against the background of manifest disease. Among a number of dermatoses, diabetic dermopathy, lipoid necrobiosis, disseminated granuloma annulare, bullosis diabeticorum, xanthomatosis, acanthosis nigricans, necrolytic migratory erythema, diabetic scleredema should be noted. Most often, patients with diabetes mellitus have dry skin and hyperkeratosis, which can cause trophic infected ulcers. As a prophylactic agent in such cases, today, SEPTOTON TM BBpharm cream with panthenol and lanolin is proposed

Narrowband UVB phototherapy as an effective treatment for disseminated granuloma annulare: A case report and review of the literature

Narrowband UVB phototherapy as an effective treatment for disseminated granuloma annulare: A case report and review of the literature

POLYGLANDULAR AUTOIMMUNE SYNDROME ASSOCIATED WITH MULTIPLE AUTOIMMUNE CONDITIONS AND ATOPIC DERMATITIS - AN UNUSUAL MANIFESTATION OF A POLYAUTOIMMUNITY PHENOTYPE.

The polyglandular autoimmune syndrome (PAS) type III is a rare condition defined as the coexistence of autoimmune thyroid disorder with other endocrine autoimmune diseases, including type 1 diabetes, without adrenal dysfunction. PAS may associate with other non-endocrine autoimmune diseases, overlapping with the multiple autoimmune syndromes (MAS). We present a case of PAS III/ MAS type 3, including autoimmune thyroiditis, autoimmune diabetes, vitiligo, lupus erythematosus, associated with adult-onset atopic dermatitis, a combination not reported previously. A 40 years old woman, registered as nurse working in dialysis unit, previously diagnosed with vitiligo, euthyroid autoimmune thyroiditis and disseminated granuloma annulare, with personal and familial history of atopic disorders, presented in our clinic for disseminated eczematous and lichenoid cutaneous rashes. She was tested positive for antinuclear, anti-double stranded DNA and anti-histone antibodies, with inflammatory syndrome and marginal lymphopenia and she was diagnosed with systemic lupus erythematosus (SLE). Subsequently, moderate hyperglycemia, positive anti-glutamic acid decarboxylase antibodies and low C-peptide level prompted the diagnosis of autoimmune diabetes. Recurrent flexural eczematous rashes, with negative epicutaneous tests but positive specific IgE tests for common allergens fulfilled the clinical criteria for the diagnosis of atopic dermatitis. The clinical, immunological and glycemic status were controlled with low doses of oral prednisone (<0.5 mg/kg), methotrexate (10mg/week), antimalarials, metformin, emollients and photoprotection. After changing her workplace, the immunosuppressive treatment could be discontinued, and the patient maintained normal immunological and biochemical profile at 6 months follow-up.This case brings a unique perspective on the evolution, associations spectrum and the management challenges of endocrine polyautoimmunity associated with atopic diathesis.

Treatment of recalcitrant granuloma annulare (GA) with adalimumab: A single-center, observational study

Generalized or disseminated granuloma annulare (GA) is therapeutically challenging. Adalimumab, a tumor necrosis factor-α antagonist, has recently been used to treat GA. We sought to evaluate adalimumab's efficacy in treating GA. We identified 7 patients with physician-verified GA who were treated with adalimumab. Primary endpoints were improvements in GA Investigator Global Assessment score and body surface area. Secondary end points included erythema and induration improvement. Seven adults, ages 51 to 77years, were included. All patients' GA Investigator Global Assessment scores improved by 2 or greater. We found significant improvements in body surface area, erythema, and induration (average improvements by 87%, 88%, and 95%, respectively). Two patients required increases in adalimumab frequency. Two others noted GA recurrence; 1 restarted adalimumab and cleared again. Adverse events were minimal. Conclusions are limited because of small sample size and observational nature of the study. Our results suggest that adalimumab could be an effective and well-tolerated treatment for GA. It is a particularly attractive therapy for patients who have generalized or disseminated GA.

Disseminated granuloma annulare in a patient with primary lymphedema

Disseminated granuloma annulare in a patient with primary lymphedema

P512 Disseminated granuloma annulare associated with Crohn's disease: a rare extraintestinal manifestation

P511 Does the location of an IBD centre impact the rates of early postoperative endoscopic recurrence after ileocecal resection in Crohn’s disease? Results from the MULTIPER database P.G. Kotze1 *, T. Yamamoto2, S. Danese3, Y. Suzuki4, I. Albuquerque5, I. Barcelos1, L. Kotze6, M. Olandoski7, F. Teixeira8, R. Silva1, M. Sacchi9, A. Yamada4, R. SaadHossne10, A. Spinelli9,11. 1Cajuru University Hospital Catholic University of Parana, Colorectal Surgery Unit, Curitiba, Brazil, 2Yokkaichi Social Insurance Hospital, IBD Unit, Yokkaichi, Japan, 3Humanitas Research Hospital, IBD Unit Gastroenterology, Milano, Italy, 4Toho University Sakura Medical Center, Internal Medicine, Chiba, Japan, 5Heliopolis Hospital, IBD unit, Sao Paulo, Brazil, 6Cajuru University Hospital Catholic University of Parana, Gastroenterology, Curitiba, Brazil, 7Catholic University of Parana, Statistics, Curitiba, Brazil, 8Gastrosaude, Colorectal Surgery, Marilia, Brazil, 9Humanitas Research Hospital, Medical Biotechnologies and Translational Medicine, Milano, Italy, 10Sao Paulo State University, Digestive Surgery Department, Botucatu, Brazil, 11Humanitas Research Hospital, IBD Surgery Unit, Milano, Italy

English

We report a Case of Disseminated Granuloma Annulare which Mimicked Sarcoidosis. A 77 year old man presented with 1 month history of closely set, shiny, skin coloured, firm smooth pruritic papules on trunk and proximal limbs. Considering the histopathological findings with well demarcated areas of degenerated collagen surrounded by histiocytes and lymphocytes, diagnosis of granuloma annulare was made and patient responded very well to oral acitretin. Disseminated papular Granuloma Annulare appears to be a distinct variant that may be difficult to diagnose.