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Acta Dermatovenerologica Croatica : ADC Aug 2023Dear Editor, Pemphigus vegetans (PV) of Hallopeau is a rare and indolent variant of pemphigus clinically characterized by vegetating lesions preceded by pustules mainly...
Dear Editor, Pemphigus vegetans (PV) of Hallopeau is a rare and indolent variant of pemphigus clinically characterized by vegetating lesions preceded by pustules mainly in flexural areas (1,2). This helps us to differentiate it from PV of Neumann, which is a more extensive and refractory disease, more alike to a pemphigus vulgaris outbreak with blisters which turn into vegetating plaques (3). We report the clinical presentation, course, and therapeutic response in a patient diagnosed with PV of Hallopeau from its early stage during a 3-year follow up. A 62-year-old man, non-smoker, presented at our clinic in July 2018 with hemorrhagic-serous crusts and fissures on the vermilion of the lower lip (Figure 1, a) and two merged circinate, sharply demarcated plaques on the right side of the groin (Figure 1, b). Plaque margins were elevated, with hypertrophic granulation tissue studded with pustules. Mucosal and cutaneous lesions persisted 6 and 4 weeks, respectively. The rest of the mucosa and skin were unaffected; the general state was good. The patient's family history for skin diseases was negative. The medical history included hypertension, atherosclerosis and hypercholesterolemia, hiatus hernia, and recent surgery (3 months prior) of an aortic abdominal aneurysm with reconstruction and synthetic graft placement. He was taking antihypertensives (fixed combination of 3 drugs, among them the ACE-inhibitor perindopril) with well-regulated blood pressure, statins, a pump-proton inhibitor, and acetylsalicylic acid. Differential blood count revealed eosinophilia. Histopathology finding showed acanthosis, suprabasal clefting with a suprabasilar bulla and acantholysis, prominent eosinophilic intraepidermal spongiosis, and heavy dermal infiltration of eosinophils and lymphocytes (Figure 2, a and b). The diagnosis of pemphigus was confirmed by direct immunofluorescence (DIF), which detected C3 deposits on the surface of keratinocytes throughout the epidermis of perilesional skin. Circulating pemphigus antibodies were detected by indirect IF. Only Dsg 3 antibodies were detected using an ELISA assay (233.23 RU/mL). After establishing the diagnosis of PV of Hallopeau, treatment with prednisolone 0.75 mg/kg/day orally in combination with adjuvant immunosuppression (azathioprine 100 mg daily) was started. Appropriate topical therapy with local steroids and antiseptic was applied. The steroid dose was titrated and gradually tapered down to the minimum required to control the disease - 10 mg. One-year remission was achieved. Azathioprine was withdrawn in October 2019 and since then the patient experienced a flare-up twice. The control of pemphigus flare-ups was achieved by a low dose of steroids (30 mg prednisolone orally). It remains debatable whether surgical trauma and radiology procedures such as angiographies (4) well as ACE-inhibitor drugs (5) triggered or aggravated the pemphigus. Early recognition and correct diagnosis of this rare type of pemphigus allows us to treat and control the disease successfully with lower doses of steroids, reducing complications to the minimum.
Topics: Male; Humans; Middle Aged; Pemphigus; Azathioprine; Skin; Eosinophilia; Blister; Prednisolone; Steroids
PubMed: 37843091
DOI: No ID Found -
BMJ Open Respiratory Research Feb 2024Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD.
DESIGN
Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only.
ELIGIBILITY CRITERIA
Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded.
DATA SYNTHESIS
The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design.
RESULTS
A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI -4.00 to 9.88, I=79.3%; %DLco -2.03, 95% CI -4.38 to 0.32, I=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DL (95% CI 2.05 to 6.79, I=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence.
CONCLUSIONS
There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD.
PROSPERO REGISTRATION NUMBER
CRD42023423223.
Topics: Humans; Azathioprine; Immunosuppressive Agents; Lung Diseases, Interstitial; Lung; Mycophenolic Acid; Enzyme Inhibitors; Observational Studies as Topic
PubMed: 38413120
DOI: 10.1136/bmjresp-2023-002163 -
Journal of Crohn's & Colitis Jul 2023
Topics: Humans; Mercaptopurine; Colitis, Ulcerative; Azathioprine; Immunosuppressive Agents; Immunologic Factors
PubMed: 37141302
DOI: 10.1093/ecco-jcc/jjad062 -
Swiss Medical Weekly Aug 2023The Swiss Autoimmune Hepatitis Cohort Study is a nationwide registry, initiated in 2017, that collects retrospective and prospective clinical data and biological samples...
BACKGROUND AND AIMS
The Swiss Autoimmune Hepatitis Cohort Study is a nationwide registry, initiated in 2017, that collects retrospective and prospective clinical data and biological samples from patients of all ages with autoimmune hepatitis treated at Swiss hepatology centres. Here, we report the analysis of the first 5 years of registry data.
RESULTS
A total of 291 patients with autoimmune hepatitis have been enrolled, 30 of whom were diagnosed before 18 years of age and composed the paediatric cohort. Paediatric cohort: median age at diagnosis 12.5 years (range 1-17, interquartile range (IQR) 8-15), 16 (53%) girls, 6 (32%) with type 2 autoimmune hepatitis, 8 (27%) with autoimmune sclerosing cholangitis, 1 with primary biliary cholangitis variant syndrome, 4 (15%) with inflammatory bowel disease and 10 (41%) with advanced liver fibrosis at diagnosis. Adult cohort: median age at diagnosis 54 years (range 42-64, IQR 18-81), 185 (71%) women, 51 (20%) with primary biliary cholangitis variant syndrome, 22 (8%) with primary sclerosing cholangitis variant syndrome, 9 (4%) with inflammatory bowel disease and 66 (32%) with advanced liver fibrosis at diagnosis. The median follow-up time for the entire cohort was 5.2 years (IQR 3-9.3 years). Treatment in children: 29 (97%) children were initially treated with corticosteroids, 28 of whom received combination treatment with azathioprine. Budesonide was used in four children, all in combination with azathioprine. Mycophenolate mofetil was used in five children, all of whom had previously received corticosteroids and thiopurine. Treatment in adults (data available for 228 patients): 219 (96%) were treated with corticosteroids, mostly in combination with azathioprine. Predniso(lo)ne was the corticosteroid used in three-quarters of patients; the other patients received budesonide. A total of 78 (33%) patients received mycophenolate mofetil, 62 of whom had previously been treated with azathioprine. Complete biochemical response was achieved in 13 of 19 (68%) children and 137 of 182 (75%) adults with available follow-up data. All children were alive at the last follow-up, and none had undergone liver transplantation. Five (2%) adults underwent liver transplantation, two of whom had a fulminant presentation. Four (2%) adults with autoimmune hepatitis died (two from liver-associated causes).
CONCLUSION
Patients with autoimmune hepatitis in Switzerland had clinical features similar to those in other cohorts. The proportion of patients diagnosed with primary biliary cholangitis variant syndrome was higher than expected. Autoimmune hepatitis was managed according to guidelines, except for the use of budesonide in a small proportion of paediatric patients. The outcomes were excellent, but the findings must be confirmed over a longer follow-up period.
Topics: Adult; Humans; Child; Female; Infant; Child, Preschool; Adolescent; Middle Aged; Male; Azathioprine; Retrospective Studies; Hepatitis, Autoimmune; Prospective Studies; Switzerland; Cohort Studies; Liver Cirrhosis, Biliary; Mycophenolic Acid; Liver Cirrhosis; Inflammatory Bowel Diseases; Budesonide
PubMed: 37769636
DOI: 10.57187/smw.2023.40102 -
Archives of Dermatological Research Nov 2023Heart transplant recipients experience high rates of skin cancer, likely due to greater length or dosage of immunosuppression. We review the impact of immunosuppressive... (Review)
Review
Heart transplant recipients experience high rates of skin cancer, likely due to greater length or dosage of immunosuppression. We review the impact of immunosuppressive medications on development of nonmelanoma skin cancer (NMSC) in heart transplant recipients. The authors searched keywords "heart transplant" and "nonmelanoma skin cancer" on PubMed in October 2022 for eligible articles available in English. Articles were selected for inclusion based on relevance to heart transplantation and NMSC. If any cited articles within included articles were related to our search they were also included. Of the 29 identified articles, 18 met the inclusion criteria with a total of 11,699 patients. Two studies found that tacrolimus and azathioprine increased the risk of NMSC. Five studies demonstrated that tacrolimus, everolimus, sirolimus, azathioprine and mycophenolate mofetil decreased the risk of NMSC. Three studies described that cyclosporine, tacrolimus, everolimus, sirolimus, azathioprine, mycophenolate mofetil and prednisone had no significant association with the development in NMSC. Two studies did not specify the correlation between immunosuppressant use and NMSC development. Ten studies did not discuss the association of immunosuppressants use with the development of NMSC. Our review highlights the commonly used immunosuppressive drugs that can impact the development of NMSC in heart transplant recipients. A management strategy in immunosuppression-associated skin cancers may ultimately involve adjusting the immunosuppressive regimen. This review serves as a summary of the most commonly used immunosuppressive drugs in heart transplant patients and their tumorigenic mechanisms to guide recommendations for dermatologic follow-up in heart transplant recipients.
Topics: Humans; Immunosuppressive Agents; Tacrolimus; Mycophenolic Acid; Azathioprine; Everolimus; Skin Neoplasms; Heart Transplantation; Sirolimus
PubMed: 37256379
DOI: 10.1007/s00403-023-02646-x -
Skin Research and Technology : Official... Mar 2024The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine,... (Review)
Review
AIMS AND OBJECTIVES
The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions.
METHOD
Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles.
RESULTS
In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%).
CONCLUSION
Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.
Topics: Humans; Methotrexate; Azathioprine; Vitiligo; Mycophenolic Acid; Minocycline; Alefacept; Cyclosporine; Adrenal Cortex Hormones; Hypopigmentation; Simvastatin; Zinc; Purines; Pyrazoles; Sulfonamides; Azetidines; Thalidomide
PubMed: 38454597
DOI: 10.1111/srt.13642 -
Contact Dermatitis Nov 2023Parthenium dermatitis is the commonest form of plant dermatitis in India, caused by the plant Parthenium hysterophorus. Systemic immunosuppressives are commonly employed... (Meta-Analysis)
Meta-Analysis Review
Parthenium dermatitis is the commonest form of plant dermatitis in India, caused by the plant Parthenium hysterophorus. Systemic immunosuppressives are commonly employed in its treatment. However, there is a relative lack of comparative head-to-head trials. This study was done to assess the relative efficacy and safety of systemic treatments in Parthenium dermatitis. We systematically reviewed all the published studies investigating the safety and efficacy of systemic treatments for Parthenium dermatitis in the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and clinical trial registries. Treatment benefit data were tabulated based on outcome measures of scoring systems. The quality of evidence for each outcome was assessed by Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria for meta-analysis. The pooled Standardized mean difference (SMD) for case series and comparative studies based on clinical severity score (CSS) for azathioprine was 4.007 (95% CI (Confidence interval): 3.141, 4.873) and 0.746 (95% CI: 0.139, 1.352), respectively. About 88.8% (95% CI: 76.8%, 100.8%, p = 0.076) of the patients had excellent or a good response to azathioprine. Our meta-analysis shows that azathioprine has the highest level of evidence in the treatment of Parthenium dermatitis.
Topics: Humans; Azathioprine; Dermatitis, Allergic Contact; Immunosuppressive Agents; Asteraceae; India
PubMed: 37634936
DOI: 10.1111/cod.14406 -
International Journal of Rheumatic... Jan 2024Azathioprine hypersensitivity can occasionally present as Sweet-like syndrome, a dose-independent side effect characterized by the unanticipated onset of macules,...
INTRODUCTION
Azathioprine hypersensitivity can occasionally present as Sweet-like syndrome, a dose-independent side effect characterized by the unanticipated onset of macules, papules, and pustules.
CASE PRESENTATION
A 35-year-old woman with systemic lupus erythematosus presented with complaints of generalized maculopapular rash, facial swelling, and bilateral lower extremity edema with a duration of 4 days and a 2-day history of constitutional symptoms within 2 weeks of the beginning of azathioprine therapy to treat existing lupus nephritis (class 2/3).
DISCUSSION
Patients who experience azathioprine hypersensitivity syndrome can present with erythema nodosum, small-vessel vasculitis, acute generalized exanthematous pustulosis, Sweet syndrome, and nonspecific dermatosis. The following signs and symptoms are used as criteria to diagnose drug-induced Sweet syndrome: (a) abrupt onset of painful erythematous plaques, (b) histopathological evidence of dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis, (c) temperature higher than 39.7°C, (d) temporal relationship between drug ingestion and clinical presentation, and (e) temporal resolution of lesions after drug withdrawal. Our patient met three out of five criteria and was diagnosed with Sweet-like syndrome.
CONCLUSION
Our case highlights the uncommonly presented azathioprine-induced Sweet-like syndrome that occurs abruptly after the commencement of the offending drug. This diagnosis can be established through basic laboratory workup and skin biopsy findings.
Topics: Female; Humans; Adult; Azathioprine; Sweet Syndrome; Skin; Lupus Erythematosus, Systemic; Erythema Nodosum
PubMed: 37401805
DOI: 10.1111/1756-185X.14817 -
Journal of Pharmacy Practice Aug 2023Macrophage activation syndrome is a life-threatening syndrome of uncontrolled immune activation with variable clinical presentation making early diagnosis difficult. It... (Review)
Review
Macrophage activation syndrome is a life-threatening syndrome of uncontrolled immune activation with variable clinical presentation making early diagnosis difficult. It is often manifested by the development of multi-organ failure due to systemic inflammatory response. Patients with ulcerative colitis (UC) on purine antimetabolites are at high risk for severe myelosuppression due to the mechanism of thiopurine toxicity which potentially contributes to the development of macrophage activation syndrome. We present a case of a 39-year-old woman with a 2-year history of UC previously treated with 6-mercaptopurine (6-MP) and recent COVID-19 infection, who was admitted to our emergency department for C. difficile infection and subsequently developed macrophage activation syndrome. This case report also raises the question of whether abrupt discontinuation of 6-MP may have contributed to the worsening of the patient's symptoms of underlying hemophagocytic lymphohistiocytosis (HLH) and her rapid deterioration. Both macrophage activation syndrome and COVID-19 infection can produce a large number of pro-inflammatory cytokines termed "cytokine storm," but a pro-inflammatory cytokine panel breakdown helps to differentiate between the two. Our case report emphasizes the importance of close monitoring of patients on purine antimetabolite therapy who present with signs and symptoms of systemic toxicity.
Topics: Humans; Female; Adult; Macrophage Activation Syndrome; Mercaptopurine; Clostridioides difficile; COVID-19; Lymphohistiocytosis, Hemophagocytic
PubMed: 35341387
DOI: 10.1177/08971900221081617 -
Rheumatology (Oxford, England) Apr 2024There is little data on renal relapse in childhood-onset LN (cLN). We investigate the incidence, predictive factors and outcomes related to renal relapse.
OBJECTIVES
There is little data on renal relapse in childhood-onset LN (cLN). We investigate the incidence, predictive factors and outcomes related to renal relapse.
METHODS
We conducted a retrospective cohort study of all cLN diagnosed at ≤18 years between 2001-2021 to investigate the incidence and outcomes related to renal relapse.
RESULTS
Ninety-five Chinese cLN patients (91% proliferative LN) were included. Induction immunosuppression was prednisolone and CYC [n = 36 (38%)] or MMF [n = 33 (35%)]. Maintenance immunosuppression was prednisolone and MMF [n = 53 (54%)] or AZA [n = 29 (31%)]. The rates of complete remission/partial remission (CR/PR) at 12 months were 78.9%/7.4%. Seventy renal relapses occurred in 39 patients over a follow-up of 10.2 years (s.d. 5.9) (0.07 episode/patient-year). Relapse-free survival was 94.7, 86.0, 80.1, 71.2, 68.3, 50.3 and 44.5% at 1, 2, 3, 4, 5, 10 and 20 years, respectively. Multivariate analysis showed that LN diagnosis <13.1 years [adjusted hazard ratio (HRadj) 2.59 995% CI 1.27, 5.29), P = 0.01], AZA maintenance [HRadj 2.20 (95% CI 1.01, 4.79), P = 0.05], PR [HRadj 3.9 (95% CI 1.03, 9.19), P = 0.01] and non-remission [HRadj 3.08 (95% CI 1.35, 11.3), P = 0.04] at 12 months were predictive of renal relapse. Renal relapse was significantly associated with advanced chronic kidney disease (stages 3-5) and end-stage kidney disease (17.9% vs 1.8%, P < 0.01). Furthermore, patients with renal relapse showed an increased incidence of infections (30.8% vs 10.7%, P = 0.02), osteopenia (38.5% vs 17.9%, P = 0.04) and hypertension (30.8% vs 7.1%, P < 0.01).
CONCLUSION
Renal relapse is common among cLN, especially among young patients, and is associated with an increased incidence of morbidity and mortality. Attaining CR and the use of MMF appear to decrease the incidence of renal relapse.
Topics: Child; Humans; Adolescent; Lupus Nephritis; Immunosuppressive Agents; Azathioprine; Retrospective Studies; Mycophenolic Acid; Treatment Outcome; Prednisolone; Recurrence; Cyclophosphamide; Remission Induction
PubMed: 37632777
DOI: 10.1093/rheumatology/kead447