Oral Azathioprine Research Articles

A Case of Recurrent Pemphigus Foliaceus Following Noncompliance to Medication.

Pemphigus foliaceus (PF) is a rare autoimmune blistering disorder requiring consistent immunosuppressive therapy for management. A 66-year-old male with a history of PF presented with worsening blisters and erosions after discontinuing medication. The patient had flaccid bullae and erosions on the face, scalp, chest, and back. Histopathology confirmed PF. Treatment with oral prednisolone, azathioprine, and reinitiation of dexamethasone-cyclophosphamide pulse (DCP) therapy led to disease remission. This case underscores the importance of adherence to immunosuppressive therapy in PF management. It also highlights the role of affordable treatment regimens in ensuring patient compliance and successful outcomes.

ANCA-Negative Pauci-Immune Crescentic Glomerulonephritis in a 26-Year-Old Postpartum Woman Treated with Oral Steroid and Azathioprine

ANCA-Negative Pauci-Immune Crescentic Glomerulonephritis in a 26-Year-Old Postpartum Woman Treated with Oral Steroid and Azathioprine

Comparison of efficacy and safety of tofacitinib and azathioprine in patients with alopecia areata and variants: a double-blind, randomized controlled trial.

Alopecia areata (AA) is an autoimmune pathology manifested by loss of hair. To evaluate and compare the efficacy and safety of tofacitinib and azathioprine in patients with AA and variants. In this double-blind randomized controlled trail (RCT) carried out at the Department of Dermatology, Medical Teaching Institute-Lady Reading Hospital (MTI-LRH), Peshawar, Pakistan, patients aged ≥ 12 years diagnosed with AA, alopecia totalis (AT) or alopecia universalis (AU) with minimum 50% scalp hair loss for a period ≥ 06 years were included. Patients were randomly assigned to receive oral tofacitinib 5mg twice daily (Group I) or oral azathioprine 2mg/kg body weight once daily (Group II). The primary endpoint was Severity of Alopecia Tool (SALT) score, evaluated at baseline and 06 months follow-up. Safety was consistently assessed during the study. A total of 104 patients underwent random allocation into either the tofacitinib group (n = 52) or the azathioprine group (n = 52). The mean (SD) age of patients was 20.23 (7.14) years and 22.26 (8.07) years, while the mean (SD) disease duration was 6.59 (4.01) years and 7.98 (4.40) years in in Group I and II, respectively. Overall, 40 (38.5%) patients were adolescents while 70 (67.3%) were male. 52 (50%) had AA, 37 (35.5%) had AT and 15 (14.5%) had AU. Mean baseline SALT score in tofacitinib group was 91.02 ± 10.21 and azathioprine group was 91.02 ± 10.63, which at 06 months follow-up improved to 14.1 ± 24.6 and 63.9 ± 33.9, respectively (difference, 11.5 points; 95% confidence interval, 38.3-61.3, p < 0.0001). Overall, no major adverse effects and no difference among the minor adverse effects in the two groups (04 adverse events for tofacitinib group and 08 for azathioprine group: p = 0.23) was observed. Efficacy of tofacitinib was significantly higher than azathioprine, whilst both drugs were well-tolerated in patients with AA and variants.

The clinical and radiological features and prevalence of Neuro-Behçet's Disease: A retrospective cohort multicenter study in Saudi Arabia

BackgroundNeuro-Behçet's disease (NBD) is defined as primary neurological involvement in patients with systemic symptoms of BD. The variety of clinical presentations seen in NBD and the long list of similar conditions make diagnosis challenging. This retrospective study aimed to estimate the prevalence and describe neurological involvement in patients with Behçet's disease who presented to King Abdulaziz Medical Cities in Jeddah and Riyadh, Saudi Arabia. MethodsThis was a retrospective, cohort study which utilized a non-probability consecutive sampling technique to include all patients diagnosed with NBD patients. All patients with BD (215) were screened for neurological symptoms. Thirty-five patients were found to be diagnosed with NBD. Outcomes were estimated using the modified Rankin scale (mRS). ResultsIn our cohort, one in six patients with BD was diagnosed with NBD. A total of 35 patients were diagnosed with NBD (mean age 27.56 ± 10.36 years; [2.88:1; Male: Female]). The main clinical features of NBD were headaches, weakness, unsteadiness, and dysarthria. The most commonly involved sites on imaging were the brainstem, diencephalon, cerebellum and basal ganglia. Oligocolonal bands were negative in all patients. Maintenance therapy most commonly included oral corticosteroids, azathioprine, and/or infliximab. Most patients received pulse corticosteroids alone when presenting with acute relapse. Half of our cohort was asymptomatic and three in four had favorable outcomes. ConclusionNBD is common among patients with BD in our population with most patients having favorable outcomes. Patients might have a wide array of symptoms which might make the diagnosis challenging.

A retrospective study describing the effective exchange of total blood plasma for disease control in the exacerbation of serpiginous choroiditis.

Serpiginous choroiditis presents with large yellow-white exudative lesions that occur near the optic nerve papillae, that progresses slowly with repeated relapses and cures. Although infection and autoimmunity have been implicated, the cause is unknown. A man was diagnosed with serpiginous choroiditis on clinical and other examinations. He started treatment with oral corticosteroids, cyclophosphamide, adalimumab, azathioprine, rituximab, and mycophenolate mofetil. Only the steroids and cyclophosphamide had a therapeutic effect. Plasma exchange was initiated, and the lesions quickly resolved. Disease control has been maintained by plasma exchange and cyclophosphamide during flare-ups in the fall and winter, suggesting that plasma exchange is effective in the treatment of serpiginous choroiditis. The reproducible response with each recurrence suggests a strong association between the disease and autoimmunity. Furthermore, that some, as yet unknown, autoantibodies are involved in the pathogenesis of serpiginous choroiditis.

The time course of complement blockage by ravulizumab in neuromyelitis optica spectrum disorder

AbstractThe classical 50% hemolytic complement test is commonly used to monitor complement function. However, its use in monitoring the effect of ravulizumab on complement assays is unknown. A 47‐year‐old man with anti‐aquaporin 4 antibody‐positive neuromyelitis optica spectrum disorder who was treated with oral prednisolone and azathioprine experienced several episodes of optic neuritis or myelitis. After his latest relapse, ravulizumab was administered to prevent relapse. Serum classical 50% hemolytic complement activity decreased below detectable levels (&lt;10 U/mL) within 1 h of ravulizumab injection. Eighteen weeks later, the patient showed no adverse events or relapse, suggesting that serum classical 50% hemolytic complement activity can monitor ravulizumab effect. In Japan, where 3.5% of the population shows a reduced response to anti‐C5 therapy, serum classical 50% hemolytic complement activity proves useful in confirming ravulizumab efficacy.

Enteric-coated Mycophenolate Sodium therApy versus cyclophosphamide for induction of Remission in Microscopic PolyAngiitis (EMSAR-MPA trial): study protocol for a randomised controlled trial

IntroductionSeveral studies have demonstrated that mycophenolate mofetil (MMF) may be an excellent alternative to cyclophosphamide (CYC) or rituximab for the induction of remission in non-life-threatening anti-neutrophil cytoplasmic antibodies associated vasculitis...

Long-term follow-up of a healthy man with endogenous Streptococcus anginosus endophthalmitis

We report the long-term follow-up of an immunocompetent patient who presented with slowly progressive endogenous endophthalmitis secondary to Streptococcus anginosus. A 46-year-old healthy man presented with a two-month history of right eye iritis. On examination, visual acuity was 20/60 with intraocular pressure of 6 mm Hg. There was a small layer of hypopyon with non-granulomatous anterior uveitis and vitritis. On funduscopy, fluffy white peripheral retinal and pre-retinal lesions were noted in superonasal periphery. The patient denied any present or past illness. Diagnostic pars plana vitrectomy was performed. Culture and polymerase chain reaction of the vitreous sample were positive for Streptococcus anginosus. Intravitreal vancomycin and ceftazidime and systemic ceftriaxone were administered. Work-up which included blood and urine cultures, chest x-ray, echocardiography and abdominal ultrasound was unyielding. Subsequently and because of persistent post-infectious inflammatory reaction, intravitreal and oral steroids were administered in addition to oral azathioprine later on. After one year of follow-up, visual acuity was 20/20 with near vision of Jaeger 3 + and no signs of active uveitis were seen. Therefore, Streptococcus anginosus should be considered in the differential diagnosis of a slowly progressive endophthalmitis also in immunocompetent individuals.

X-Linked Lymphoproliferative Syndrome: A Spectrum of Clinical and Immunological Profile and Novel Pathogenic Variants from Chandigarh, India

Introduction: X-linked lymphoproliferative syndrome (XLP) is a rare primary immune deficiency. Two types of XLP have been described: XLP-1 and XLP-2. Methods: We found 7 patients with XLP (3 had XLP-1 and 4 had XLP-2) after reviewing the data from Pediatric Immunodeficiency Clinic from 1997 to 2021. Results: Mean age at diagnosis was 3.8 years, and mean delay in diagnosis was 2.6 years. Five patients had recurrent episodes of infections. Four patients developed at least one episode of hemophagocytic lymphohistiocytosis (HLH) (2 with XLP-1 and 2 with XLP-2). Of these, 2 had recurrent HLH (both with XLP-2). Epstein-Barr virus (EBV) infection was detected in 2 (1 with XLP-1 and 1 with XLP-2). Both these patients had HLH. One child with XLP-2 had inflammatory bowel disease. Hypogammaglobulinemia was seen in 3 (2 with XLP-1 and 1 with XLP-2). Genetic analysis showed previously reported variants in 5, while 2 had novel variants (one in exon 7 of XIAP gene [c.1370dup p.Asn457Lysfs Ter16] and other had splice site variant in intron 1 of SH2D1A gene [c.138-2_138-1insG]). Episodes of HLH were managed with intravenous immunoglobulin (IVIg), methylprednisolone, oral prednisolone, cyclosporine, and rituximab. Inflammatory bowel disease was managed using oral prednisolone and azathioprine. One patient underwent haploidentical hematopoietic stem cell transplantation. One child with XLP-2 and WAS died because of fulminant pneumonia. Discussion/Conclusions: XLP should be considered as a strong possibility in any patient with features of HLH, repeated infections with hypogammaglobulinemia, persistent EBV infection, and early-onset IBD.

Bullous pemphigoid associated with the use of DPP4 inhibitors: A case series

Dipeptidyl-peptidase 4 (DPP-4) inhibitors are one of the most commonly used anti-diabetic drugs because of their established safety and efficacy. Bullous pemphigoid which is an autoimmune blister skin disorder associated with DPP-4 inhibitors is a recognized adverse drug reaction (ADR) reported in some Southeast Asian Nations but has not been reported earlier from India. It is an uncommon, serious treatment with emergent adverse effects. Here, we report a series of five cases of DPP-4 inhibitor Linagliptin-induced bullous pemphigoid reaction in Type 2 diabetes mellitus patients. We are reporting five cases that showed various clinical manifestations in terms of gender (males 4), duration of diabetes (average 7.2 years), glycemic control (average HbA1C 6.7%), and latency period (average 3.6 weeks) for development of the ADR. Quality of life and treatment satisfaction were severely impacted by this ADR. Withdrawal of Linagliptin, use of topical and oral steroids and immunosuppressant like azathioprine were prescribed and effective for improving the lesions of all the cases. As per the World Health Organization-Uppsala Monitoring Center scale, causality was established as “probable” for all the cases. This case series serves to bring to the notice of prescribers regarding this important cutaneous ADR with the use of Linagliptin. This case intends to improve awareness among clinicians regarding the possibility of this cutaneous ADR among diabetic patients to facilitate early diagnosis and intervention.

Current Therapeutic Options in Active Moderate-to-Severe Thyroid-Associated Ophthalmopathy

Abstract Active moderate-to-severe TAO is a disease, the treatment of which requires a multidisciplinary team, an individualized approach and strict follow-up, yet it is often suboptimal. Recent knowledge about the pathogenesis of the disease and the randomized controlled trials conducted in recent years made it possible to use new therapeutic combinations and biological agents. The currently recommended first-line therapy for active moderate-to-severe TAO is the combination of intravenous glucocorticoids (GCs) in moderate doses and mycophenolate or, in more severe cases, a high-dose GC treatment alone. There are several options for second-choice therapy, if needed: a new course with GCs, combination of orbital radiotherapy and GCs (preferably intravenous), cyclosporine and oral GCs, azathioprine and oral GCs, rituximab, tocilizumab or teprotumumab. The clinical manifestations of TAO should also be considered when choosing second-line treatment. Thus, for example, teprotumumab best affects diplopia, orbital radiotherapy – visual disturbances and diplopia, while intravenous GCs, mycophenolate, cyclosporine, rituximab and tocilizumab – the inflammatory manifestations of TAO. However, the question of the availability of the new drugs in routine clinical practice remains unsolved.

Efficacy of Combined Initial Treatment of Methotrexate with Infliximab in Pediatric Crohn's Disease: A Pilot Study.

The combination of antitumor necrosis factor-alpha (TNF-α) agents with immunomodulators (IMMs) is a common treatment for pediatric Crohn's disease (CD). Although methotrexate (MTX) can be a first-line medication as an IMM, most clinicians in real-life practice, especially in South Korea, are more familiar with thiopurines. This study aimed to compare the efficacy and immunogenicity of MTX and azathioprine (AZA) as concurrent therapies for pediatric CD. In this pilot study, 29 newly diagnosed pediatric patients with moderate-to-severe CD were randomized to receive either MTX (n = 15) (15 mg/body surface area (BSA) per week) or oral AZA (n = 14) (0.5 mg/kg per day) in combination with Infliximab (IFX). The primary outcomes were the proportion of patients in endoscopic, biochemical, and transmural remission after 14 and 54 weeks of IFX therapy. The trough levels (TLs) of IFX and anti-drug antibody (ADA) levels were also compared. Among the 29 patients, there were no significant differences in the biochemical (p = 1.0 at week 14, p = 0.45 at week 54), endoscopic (p = 0.968 at week 14, p = 0.05 at week 54), or transmural (p = 0.103 at week 54) remission rates between the two medications during the concurrent therapy. Additionally, the trends in the IFX trough and ADA levels over time during the treatments were similar for both medications, with no significant differences (p = 0.686, p = 0.389, respectively). The MTX showed comparable efficacy to the AZA in pediatric CD patients with moderate-to-severe disease. This effectively maintained adequate IFX levels and reduced ADA production. Therefore, although additional large-scale clinical trials are needed, this study demonstrated that either MTX or AZA can be selected as IMMs in the concurrent treatment of pediatric CD, depending on individual medical institutions' circumstances.

Different clinical phenotypes of AQP4-IgG positive NMOSD in two first degree relatives

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) are autoimmune inflammatory disorders of the CNS in which patients have severe relapses of optic neuritis and myelitis. Aquaporin-4 antibody (AQP4-IgG) positive NMOSD has not been reported in members of the same family in Sub Saharan Africa. We report the uncommon scenario in which both a Ugandan HIV positive woman and her HIV negative daughter were diagnosed with AQP4-IgG positive NMOSD. We discuss pathogenic mechanisms that may underlie familial presentation of AQP4-IgG positive NMOSD.Case PresentationCase 1, a 54-year-old female teacher with a 20-year history of HIV infection and virally suppressed on Tenofovir, Lamivudine and Dolutegravir HAART regimen, presented with 8 months of progressive quadriparesis and urinary incontinence with a T6 sensory level. She had gadolinium enhancing longitudinally extensive transverse myelitis on MRI and was AQP4-IgG positive on serum studies. She received IV Methylprednisone 1 g daily for 3 days as a pulse and was continued on tapering doses of oral Prednisone with maintenance doses of Azathioprine. She showed slow improvements in limb motor function. Her daughter, case 2, is a 35-year-old HIV negative nutritionist, independently ambulant, with no known comorbidities or precedent autoimmune disease. She presented 1 year before her mother’s AQP4-IgG positive NMOSD diagnosis with 7 months history of bilateral visual loss of rapid onset, with gadolinium-enhancing optic nerves on Brain and orbit MRI, in keeping with bilateral optic neuritis. She was AQP4-IgG positive on serum studies. She stabilized on tapered doses of oral Prednisone and continues daily oral Azathioprine with moderate improvement in her vision and no further relapses as yet.ConclusionsWe add to existing literature and hypothesize that NMOSD appears to show a complex genetic background. To our knowledge, this is the first report in Sub-Saharan Africa, of familial AQP4-IgG positive NMOSD presenting with clinical heterogeneity between first degree relatives. A better understanding of the pathogenic mechanisms involved, including genome wide studies for particular risk loci for familial NMOSD, will be pivotal for future preventative and therapeutic strategies.

A Rare Case of Sarcoidosis Presenting as an Isolated Breast Mass and Pain: A Case Report and Literature Review.

BACKGROUND Sarcoidosis is a benign systemic granulomatous disorder of unknown etiology that affects multiple organs. Patients diagnosed with sarcoidosis usually present with nonspecific symptoms: fatigue, fever, weight loss, and respiratory symptoms such as cough and dyspnea; 50% of the patients are asymptomatic at the time of diagnosis. In 90% of patients, sarcoidosis targets hilar and mediastinal lymph nodes. In rare cases, it presents solely in the breast with no other symptoms. The diagnosis is established based on compatible clinical and radiological findings and supported by histological evidence in 1 or more organs of non-caseating epithelioid cell granulomas in the absence of organisms or particles. CASE REPORT We herein present a unique case of a 27-year-old woman who presented with pain and swelling in her left breast. On examination, the left breast revealed multiple, firm-hard, and tender masses. Breast ultrasound showed large loculated focally dilated ducts with significant periductal vascularity and inflammation. Fine-needle aspiration (FNA) showed an inflammatory process with granulomatous formation. An ultrasound-guided core biopsy, which was histologically consistent with granulomatous mastitis, and elevated angiotensin-converting enzyme (ACE) levels confirmed a diagnosis of sarcoidosis. The patient was started on IV steroids followed by oral prednisolone and azathioprine. During treatment, the mass size decreased and the pain substantially improved. CONCLUSIONS It is important to consider sarcoidosis in a patient who presents with only pain and swelling in the breast to ensure early diagnosis and initiate treatment, improving the patient's overall prognosis.

A Comparative Study on the Efficacy and Safety of Using Azathioprine Alone, Combining It with Narrow Band (UVB) and to Oral Minipulse Steroids Plus NB-UVB in Stabilizing Active Non-Segmental Vitiligo

Abstract Background Vitiligo is an acquired, non-contagious, pigmentary disease resulting from the loss of melanocytes from skin, hair and mucous membranes. The pathogenesis of vitiligo is still not fully understood and mounting evidences have suggested that it might be related to autoimmunity and oxidative stress. Aim of the Work To evaluate the efficacy and safety of AZA in stabilizing disease progression of active vitiligo, compare it with its combined therapy with NB-UVB and with OMP steroids combined with NB-UVB. Patients and Methods This study included Forty five patients complaining of active non-segmental vitiligo divided into three groups: Group (A): 15 patients received narrow band therapy with oral mini-pulse steroid therapy (dexamethasone) as a single dose on two consecutive days repeated every week for 3 months, Group (B): 15 patients received narrow band therapy (same regimen as in group A) combined with oral azathioprine 50 mg twice daily for 3 months, and group (C): 15 patients received oral azathioprine alone for 3 months. Results Evaluation of treatment response was done at 4, 8 and 12 weeks of treatment by assessing the onset of stoppage of disease activity as well as the onset of repigmentation and its extent using VES, VES plus and VIDA scores. Encountered side effects were also documented. Conclusion Both oral minipulse steroid therapy and azathioprine are effective in stopping the activity of vitiligo, either as monotherapy or better combininig with NBUVB, though azathioprine being inferior to OMP steroid therapy in arresting disease progression and inducing re-pigmentation. Thus, it can be used as a good alternative when there is contraindication to use systemic steroids.

CD14 Mouth ulcer mayhem secondary to dental fillings

Abstract Dental amalgam contains mercury, which may cause an uncommon lichenoid allergic contact dermatitis (ACD) affecting the oral mucosa in direct contact with the amalgam filling. Distinguishing a lichenoid amalgam reaction from oral lichen planus is challenging, both clinically and histopathologically. This case illustrates the important role that patch testing to dental materials can play in providing a simple answer in the management of resistant cases of mouth ulceration, protecting patients from exposure to potentially toxic immunosuppressive treatments. A 64-year-old woman presented with a 5-year history of oral ulceration affecting the buccal mucosa and tongue bilaterally. These ulcers were persistent, very painful and bled intermittently, causing a significant adverse effect on her quality of life. She worked as a manager at a local wildlife sanctuary, and hobbies included walking, writing and artwork. An incisional biopsy taken from an ulcer in the left buccal mucosa demonstrated a dense lichenoid inflammatory cell infiltrate. The oral surgical team treated her for presumed ulcerative oral lichen planus with multiple treatments, including topical steroids, high doses of oral prednisolone, hydroxychloroquine, mycophenolate mofetil and azathioprine. She gained only very minimal benefit. The oral surgeons then requested dermatological advice for the next potential treatment option, which was suggested to be rituximab. At this point, the surgeons noticed that the ulcers seemed to be most prominent at sites of the patient’s longstanding amalgam fillings and she was referred for patch testing. Patch tests were performed to the British Standard series, medicaments series and oral and dental series. Positive reactions were noted to both amalgam (D2+/D4+) and mercury (D2+/D4+). The patient had her amalgam fillings replaced with white acrylate fillings, and her oral ulceration completely healed without the need for any further immunosuppression. Clinically and histologically, lichenoid ACD secondary to dental fillings can be indistinguishable from idiopathic oral erosive lichen planus. However, the proximity of ulceration to dental filling materials should always raise the possibility of a lichenoid ACD and trigger referral for patch testing, preferably prior to systemic medications being tried. This case highlights the importance of patch testing in patients with localized, asymmetrical, difficult-to-treat oral ulcers adjacent to amalgam fillings, which could spare the patient from exposure to potentially harmful immunosuppressive treatments.

Late-Onset Neuromyelitis Optica Spectrum Disorder Mimicking a Non-Arteritic Anterior Ischemic Optic Neuropathy-Case Report.

A 60-year-old white woman presented to the emergency department with painless decrease of visual acuity in the left eye (LE). The diagnosis of a non-arteritic anterior ischemic optic neuropathy in the LE was established based on the clinical picture and the results of static perimetry, fluorescein angiography, visual evoked potential, and magnetic resonance imaging (MRI) of the brain and orbit. Six months later, the patient reported visual impairment in the right eye (RE). Best corrected visual acuity (BCVA) in the RE was 5/10. Gadolinium-enhanced MRI showing inflammation of both optic nerves and the optic chiasm in correlation with positivity for immunglobulin G antibody against aquaporin-4 led to the diagnosis of late-onset neuromyelitis optica spectrum disorder. High-dose intravenous methylprednisolone therapy followed by oral tapering was administered and oral azathioprine was started to reduce the risk of further relapse. At discharge, BCVA was 5/5 in the RE. The patient remains under the care of neurology and ophthalmology clinics, with no recurrences for two years. The possibility of neuromyelitis optica spectrum disorder with optic neuritis in older patients is important in the differential diagnosis of ischemic optic neuropathy.

A case of bullous pemphigoid developing under treatment with benralizumab for bronchial asthma.

Bullous pemphigoid (BP) is an autoimmune disease characterized by itchy erythema and tense blisters on the whole body. Recent reports have unveiled the pathogenic roles of eosinophils in BP (e.g., dermal-epidermal separation, generation of pruritus). Thus, eosinophils are considered a therapeutic target. Benralizumab is an anti-IL-5 receptor alpha (IL-5Rα) monoclonal antibody (mAb) that is widely used to treat severe eosinophilic asthma. By affecting IL-5Rα, benralizumab depletes eosinophils and basophils due to apoptosis through antibody-dependent cell-mediated cytotoxicity. The efficacies of benralizumab and other biologics, including bertilimumab (anti-eotaxin-1 mAb) and mepolizumab (anti-IL-5 mAb), were evaluated in several clinical trials. Also, reslizumab, an anti-IL-5 mAb, was reported as a successful treatment option in a case of BP. We present a case of severe asthma treated with benralizumab at 8-week intervals for 3 years before BP developed. Histologically, subepidermal blisters without eosinophilic infiltration were observed. Methylprednisolone pulse therapy followed by 40 mg/day (1 mg/kg/day) of oral prednisolone (PSL) was initiated, but the skin lesions worsened. Additional intravenous immunoglobulin and oral azathioprine enabled the oral PSL to be tapered. The benralizumab was discontinued after the onset of BP because the asthma did not worsen. To the best of our knowledge, there have been no reports of BP developing during anti-eosinophil therapy. BP may occur paradoxically via various pathways during treatment with drugs that are typically effective against BP.

Emerging Systemic Treatments for Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin disease which results from a complex, multifaceted interaction between environmental factors in genetically predisposed patients. Epidermal barrier impairment, alteration of the cutaneous microbiota, effect of external antigens, neurosensory dysfunction, and inflammatory and immune dysregulation all play a pivotal role in inducing and maintaining AD lesions. AD significantly impacts the patient's quality of life and general well-being and is often associated with anxiety and/or depressive symptoms. Classical treatment options include topical corticosteroids and calcineurin inhibitors, phototherapy, and systemic immunosuppression with oral corticosteroids, cyclosporine, methotrexate, and azathioprine in more severe cases. A turning point in facing AD was accomplished when the efficacy and safety of dupilumab, a monoclonal antibody targeting the interleukin (IL)-4 receptor α subunit, led to its approval for the treatment of moderate-to-severe or severe AD in children, adolescents, and adults. Subsequently, a more extensive understanding of AD etiology and pathogenesis has allowed the development of several topical and systemic novel therapy options. Most of these drugs are monoclonal antibodies which interfere with the type2 inflammatory cascade, especially its key cytokines IL-4 and IL-13, or its downstream Janus kinase signaling pathway. However, considering the relevance of other subtypes of Thelper (Th) cells, such as Th1 and Th22, and the important role of specific cytokines (IL-31) in generating pruritus, the horizon of potential therapeutic targets has widened extremely. In this review, we aim to present the most promising systemicagents currently under investigation and illustrate the most significant aspects of their efficacy, safety, and tolerability.

An unusual clue in the diagnosis of primary Sjogren’s syndrome

Sjogren’s syndrome (SSj) is a chronic autoimmune disease mainly targeting the exocrine glands, but sometimes associating extra-glandular manifestations. Xerosis, purpura, Raynaud’s phenomenon, cutaneous vasculitis, annular erythema are the main forms of skin involvement. A 26-year-old female patient was admitted for diffuse erythematous rash and angioedema, xerophthalmia and symmetrical arthralgia of hand joints. Anti-nuclear antibodies, anti-SSA and anti-Ro52 antibodies were identified, Schirmer’s test was positive, thus the diagnoses of primary SSj and associated urticarial vasculitis were established. Treatment with oral methylprednisolone, azathioprine and hydroxychloroquine was initiated, with favorable response over the next week. Patients with primary SSj that develop cutaneous vasculitis, lymphadenopathies or lymphopenia may be at risk for additional extra-glandular manifestations, including non-Hodgkin lymphoma.