Treatment strategy in chronic lymphocytic leukemia with symptomatic central nervous system involvement : a case reportAuthor: Rosina Dewaide, M.D. University Hospital Antwerp: Universitair Ziekenhuis Antwerpen Antwerpen, BELGIUMCo-author: Kirsten Saevels, , M.D. University Hospital Antwerp: Universitair Ziekenhuis Antwerpen Antwerpen, BELGIUMCorresponding author: Rosina.Dewaide@uza.beThe author and co-author state that they have no conflict of interest.Written informed consent was obtained from the patient to publish this report in accordance with the journal’s patient consent policy.
Introduction Fibromyalgia (FM) is defined as a “syndrome of central sensitisation with dysfunction of the neuronal circuits involved in the perception, transmission and processing of nociceptive afferents, with pain predominantly expressed in the musculoskeletal system”1. It is an incurable syndrome of unknown origin with signs and symptoms often similar and overlapping with those of other syndromes. This condition, unfortunately with high frequency, delays its diagnosis. The pathogenetic mechanism underlying the clinical picture is alteration of the nociceptive system.Several hypotheses have been proposed concerning the pathogenesis of FM and the management of FM patients requires a multidisciplinary approach.Accumulating evidence suggests that hyperbaric oxygen therapy (HBOT) is a non-invasive modality with lasting efficacy to treat FM2. HBOT is defined by the Undersea and Hyperbaric Medical Society (UHMS) as a treatment in which a patient intermittently breathes 100% oxygen while the treatment chamber is pressurised to above sea level pressure (1 atmosphere absolute, 1 ATA = 760 mmHg)3. HBOT is able to induce many interesting effects on plasma oxygen concentration. Based on Henry’s Law, increased pressure will cause more gas to go into solution, and therefore,more oxygen will be transported in the plasma. As a result a lot of oxygen becomes available for the microcirculation, resulting in significant improvement of all metabolic parameters, which have also been shown in several works to influence neurological functions4. We report about a case of woman affected by FM and treated with HBOT as adjuvant, experimental and non conventional therapy.Case PresentationIn January 2021 a 54-year-old Caucasian woman with a negative medical past history reported pain in her left arm 24 hours after receiving the first dose of the Pfizer SARS-Covid 19 vaccine. Localised pain in the injection zone (the triceps muscle of the left arm) was accompanied by the onset of high fever (40°C), intense headache with vomiting and abdominal pain. After 48 hours there was defervescence with return to normo-thermia but progressive appearance of fatigue. Subsequently patient report a relief of pain in the left arm with progressive development of constant, severe and persistent pain in occipital and back neck area, low back and legs with a marked sense of heaviness in the lower limbs. The patient also complained of progressive difficulty in walking, for which the use of nordic walking sticks was necessary. Furthermore, she reported stiffening of the facial muscles with pain defined as intense, mental fogginess, severe short-term memory involvement and progressive depression, symptoms that had undoubtedly caused a significant impairment in her quality of life.The patient underwent routine blood sample tests (blood count, ESR, PCR, protein electrophoresis, AST, ALT, gamma GT), as well as more specific immuno-enzymatic tests (serum kappa and lambda chains, IgG, IgA, IgM, anti-nuclear antibodies, ENA, ANA with subclasses). The exams showed no values outside the standard range. Only a slight increase in ESR and a reduction in 25-OH-vitamin D levels was shown. The patient also performed total body CTs, spine MRI, femoral and lumbar bone densitometry from which no structural morphological alteration was highlighted except for an initial picture of osteoporosis. The exclusion of inflammatory disease, although some rheumatic diseases could coexist, suggested a possible diagnosis of FM and thus rheumatologists have sought its diagnostic criteria5. The persistence of pain was well over 3 months (the patient reported the onset of symptoms about 18 months ago).The following questionnaires were administered: Widespread Pain Index (WPI), Symptom Severity Scale (SSS), Revised Fibromyalgia Impact Questionnaire (FIQR), Pittsburgh Sleep Quality Index (PHQI), Generalized Anxiety Disorder Screener (GAD-7), Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F). The scores reported from each individual questionnaires carried out before the start of HBOT were as follows: WPI=18, SSS=10, FIQR=96, PHQI=17, GAD-7=14, FACIT=12.Thus she started a multidisciplinary therapeutic course based on antalgic therapy, physiotherapy, psychological support, relaxation techniques and healthy nutrition.Among the various therapies, HBOT was indicated as an experimental non-conventional treatment. The patient underwent forty sessions of HBOT at 2.4 ATA (absolute atmospheres), total oxygen time 60 minutes per session, once a day, five times a week, performed at the multi-place chamber (Sistemi Iperbarici Integrati-Camera Iperbarica Mod 2000) of the Hyperbaric Medicine Centre of ARNAS Ospedale Civico Di Cristina Benfratelli, Palermo, Italy. Therapy started in the first week of September and ended in mid-November 2022. Throughout each session, the patient showed stable vital parameters (blood pressure, heart rate, oxygen saturation and body temperature). Blood tests, markers of flogosis and haematochemical examinations carried out at mid term and at the end showed no change in values outside the normal range.The patient underwent 40 sessions of HBOT. The clinical improvement achieved was evident and affected all symptom areas reported before treatment. In particular, there was a complete recovery of mobility with the avoidance of walking sticks, an increase in muscular strength evidenced by the ability to climb several flights of stairs and to walk long distances independently. The patient reported a drastic reduction in pain symptoms evident from the moment she woke up in the morning, a significant improvement in sleep quality, previously reported as light, non-restorative and with multiple breaks. The highly debilitating sense of fatigue was reported after treatment as markedly reduced and in any case easily manageable. In addition, a significant change in cognitive abilities was reported, with disappearance of mental fogginess and recovery of short-term memory. In summary, there was a significant improvement in quality of life with the disappearance of the depression into which the patient had plunged, a condition confirmed by psychological advice at the end of the hyperbaric treatment. The scores reported by each individual test at the end of HBOT are shown below: WPI=6, SSS=3, FIQR=13, PHQI=2, GAD-7=3, FACIT=42.
The Role of multidetector CT scan in the Management of Prosthetic Aortic Valve thrombosis: A Case Report.Sheriff N Dodoo, MD1; Christelle Yakana Moyine, MD2; Alicia Agyemang-Sarpong3; Abdullah Ismail, MD2; Nina Le, DO2; Falgun Patel, MD4; Nima Ghasemzadeh, MD4; Ronnie Ramadan, MD4; Khaja Salahuddin Mohammed, MD4; Glen Henry, MD4; Ioannis Parastatidis, MD PHD5Georgia Heart Institute, Northeast Georgia Medical Center, 743 Spring Street NE, Gainesville, GA 30501, U.S.A. Email: email@example.comDepartment of Internal Medicine, Northeast Georgia Medical Center, 743 Spring Street NE, Gainesville, GA 30501, U.S.A.Postgraduate Medical Education, Harvard Medical School, Boston Massachusetts, USAGeorgia Heart Institute, Interventional Cardiology, Northeast Georgia Medical Center 200 S Enota Dr NE, Gainesville, GA 30501, U.S.A.Georgia Heart Institute, Northeast Georgia Medical Center 100 S Enota Dr NE, Gainesville, GA 30501, U.S.A.
Introduction:Snapping at the lateral knee can be caused by a variety of pathologies involving surrounding soft tissue structures such as the popliteus, semitendinosus and/or gracilis tendons, IT Band syndrome, lateral meniscus tears, or rheumatoid nodules.1-4snapping In rare instances, lateral knee pain may also be caused by the distal tendon of the biceps femoris long head shifting over the fibular head.5-6 Regardless, the various differential diagnoses should be properly ruled out by a careful history, a detailed physical exam, and advanced imaging.Few cases of snapping biceps femoris tendons have been recorded in the literature across various case reports. Causes of the snapping biceps femoris tendon have been attributed to anomalous insertions (most prevalent), 7-16 tendon subluxation,17-18 abnormalities of the fibular head,19-23 or secondary to trauma. 6, 24 Conservative treatment is usually attempted first and consists of physical therapy and anti-inflammatory medications as needed. Surgery, which is usually the last resort and the most effective, consists of resecting the anomalous tendon insertion or correcting any fibular deformities.In this report, we present a patient with lateral knee pain from an accessory insertion of the snapping biceps femoris tendon and discuss surgical exploration and repair. The patient was informed that his case would be submitted for publication and he provided consent.
Anesthesia using remimazolam during coronary artery bypass surgery in a patient with decreased left ventricular functionShingo Narumi, Yusuke Ishida, Sae Igarashi, Shunya Sekiguchi, Aya Kawachi, and Mikiko TominoDepartment of Anesthesiology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, JapanCorresponding author: Yusuke IshidaDepartment of AnesthesiologyTokyo Medical University6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, JapanTel.: +81-03-3342-6111; Fax: +81-03-5381-6650Email: firstname.lastname@example.org
Introduction:To prevent acute or chronic allograft rejection, recipients of kidney transplants are needed to take immunosuppressive for the rest of their lives. However, their compromised immune system put them at risk for opportunistic infections as well1. Infection with the varicella-zoster virus (VZV) is an unusual in recipients of kidney transplants at a frequency rate from 1% to 11%, but the severity is more significant in transplant patients compared to the overall population 2, 3. Fever and a self-limiting rash on the skin and occasionally the mucosa may be the present symptoms of varicella infection. Additionally observed symptoms include headache, malaise, and appetite loss. The rash starts off as macules, quickly develops into papules and then goes through a vesicular stage and crusts over the lesions. After one to two weeks, crusts flake off4. Disseminated herpes zoster (HZ) in kidney transplant recipients can result in a very high overall mortality rate of up to 30% 5.Here we describe a 23-year-old male patient with a history renal transplant who presented to the emergency department with complaint of high grade fever, chills and generalized rash for 5 days.
Introduction Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome that is associated with a high mortality rate. HLH is characterized by hemophagocytosis and histiocytic proliferation (1). Primary HLH has a familial pattern and secondary HLH is reactive and also called macrophage activation syndrome (MAS). This type of HLH is usually acquired following autoimmune diseases, infection, and malignancy (2).The prevalence of HLH is not completely measurable because the diagnosis of this disease is hard and there are other comorbid diseases at the time of diagnosis. In a study that was done in Sweden from 1987 to 2006, the prevalence of HLH was 1.5 per million (3).The manifestations of HLH are fever and cytopenia. The diagnosis of HLH is made by clinical suspicion of physicians. The criteria for diagnosis of HLH include fever; splenomegaly; cytopenia (affecting at least two of three lineages in the peripheral blood); fasting triglyceride levels ≥3 mmol/L and/or fibrinogen level ≤1.5 g/L; serum ferritin level ≥500 ng/ml; CD25 level ≥2400 U/ml; decreased or absent natural killer (NK) cell activity; or hemophagocytosis in bone marrow, spleen, or lymph nodes (4).Adult-onset Still’s disease (AOSD) is an autoimmune disorder that can predispose patients to HLH. The co-incidence of AOSD and HLH is rare (5).In this report, we present a woman with a co-incidence of AOSD and HLH.
INTRODUCTIONGranulomatosis with polyangiitis (GPA) is a rare form of small vessel vasculitis characterized by multisystem necrotizing granulomatous lesions with different organs involvements such as the central nervous system, urinary tract, gastrointestinal tract, skin, and even eye (1-3). The main pathological characteristic of GPA is the positivity of autoantibodies against cytoplasmic components of neutrophil cells or C-ANCA as well as proteinase-3 (PR3) over-activation (4). Due to the multisystem involvement nature, the diagnosis of GPA is difficult. Additionally, GPA may overlap with other clinicopathological conditions such as infections, autoinflammatory disorders, connective tissue diseases, and even neoplasms (5,6). In this regard, the involvement of salivary glands is a very rare phenomenon. Herein, we described a case of GPA with submandibular salivary gland involvement followed by reviewing the literature on similar cases.
Report of Two cases of Schaaf-Yang Syndrome: Same Genotype, Different Phenotype Ana Maria Rodriguez,a MD, Katherine Schain,a MS, CGC, Parul Jayakar,aMD,MS,FACMG, Meredith S. Wright,b,c PhD., Shimul Chowdhury,b PhD., Daria Salyakina,ePhD.a Division of Genetics and Metabolism, Nicklaus Children’s Hospital Pediatric Specialists, Miami, (FL,) USA.b Rady Children’s Institute for Genomic Medicine, San Diego, (CA,) USA. c Keck Graduate Institute, Claremont, (CA,) USA. d Personalized Medicine & Health Outcomes Research, Nicklaus Children’s Hospital Pediatric Specialists, Miami, (FL,) USACorresponding Author: Ana Maria Rodriguez BarretoDivision of Genetics and Metabolism, Nicklaus Children’s Hospital Pediatric Specialists, Miami, (FL,). 3100 SW 62nd Avenue, Miami, FL, 33155, USA. Tel: 786-624-4717. Fax : 786-624-4704. E-mail: email@example.comCo-authors: Katherine Schain: Katherine.Schain@Nicklaushealth.orgParul Jayakar: Parul.Jayakar@Nicklaushealth.orgMeredith S. Wright: MWright3@rchsd.orgShimul Chowdhury: firstname.lastname@example.orgDaria Salyakina: Daria.Salyakina@Nicklaushealth.orgConflicts of Interests Statement: We know of no conflicts of interests associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome. As Corresponding Author, I confirm that the manuscript has been read and approved for submission by all the named authors.Informed Consent : Written informed consent was obtained from both patients parents.Ethics Declaration: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by The Institutional Review Board (or Ethics Committee) of Nicklaus Children’s Hospital Pediatric Specialists.
Title: AngioinvasiveTrichophyton rubrum associated necrotizing fasciitis in an immunocompromised patientAuthors: Michael J. Davis, DO, MPH1-3*; Katelyn J. Rypka, BS3-6*; Alexandra K. Perron, BA6; John Keilty, BS6; Benjamin Wils, MS 6; Joshua Levine, BA 6; Anthony T. Rezcallah, MD7-8; Robin Solomon, MD9; Noah Goldfarb, MD3-5†; Anjum Kaka, MD1, 3†Affiliations:1Department of Infectious Disease, Minneapolis VA Health Care System, Minneapolis, MN2Department of Infectious Disease, University of Minnesota, Minneapolis, MN3Department of Internal Medicine, Minneapolis VA Health Care System, Minneapolis, MN4Department of Dermatology, Minneapolis VA Health Care System, Minneapolis, MN5Department of Dermatology, University of Minnesota, MN6University of Minnesota Medical School, Minneapolis, MN7Department of Surgery, Minneapolis VA Health Care System, Minneapolis, MN8Department of Surgery, University of Minnesota, Minneapolis, MN9Department of Pathology, Minneapolis VA Health Care System, Minneapolis, MN*These authors contributed equally†These authors contributed equally
TITLE OF CASE Multiple Emergency Department Encounters for Acute Musculoskeletal Presentation with an Existing Mental Health Diagnosis SUMMARY Reconceptualising acute Musculoskeletal (MSK) injuries with both stress- and tissue- based factors is required to consider prior influences of mental health disorders on acute persistent musculoskeletal pain presentations involving an extremity. This report highlights repeated emergency presentations for acute persistent musculoskeletal pain involving an extremity for an individual in their 20s living with mental health diagnoses ranging across Depression, Mood Disorders and an eating disorder. This person also had mental health related inpatient admissions that were not captured under the retrospective record review for a large district hospital emergency department using the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) classification system. This case report attempts to demonstrate that improving the understanding of pre-existing vulnerabilities and mental health diagnoses may assist with informing healthcare design to develop specialised care pathways for acute injury presentations with triage settings. BACKGROUND Acute MSK pain represents a common cause for seeking emergent health care (1),(2). While the majority of acutely injured people should expect to recover spontaneously, 50% will transition from acute to chronic pain and disability (3, 4). Data from robust clinical trials (5) and prevalence studies have failed to enable us to adequately identify individuals at risk of delayed recovery from MSK injury, and interventions targeting known risk factors have yielded, at best, only modest effects (6, 7). Furthermore, the most recent output from the global burden of disease in 2019 suggest MSK conditions are a leading cause of civilian years lived with disability. Alarmingly, this has not changed since 1990, suggesting research has had little effect on reducing the burdens of acute and chronic MSK conditions. Perhaps critical to this long-standing problem is that research has not generated new mechanistic knowledge into why some people recover and others do not following their acute MSK presentation. (8). Perhaps reconceptualising the acute MSK injury (be it a slip-and-fall, motor vehicle collision, fracture, muscle strain affecting the spine or extremities) as both a stress- and tissue-based injury is required to integrate and consider how pre-existing diatheses such as mental health disorders (9) influence the process of recovery. By identifying patients who may be vulnerable to costly negative chronic outcomes, appropriate early screening tools and preventative treatments can be offered to improve clinical outcomes and avoid harmful secondary effects, such as opioid dependency, stigma, poor return to work outcomes, withdrawal from valued life roles, long-term reliance on ineffective and costly management options and repeat emergency department (ED) encounters. For example, people living with mental health conditions tend to experience adverse physical health outcomes and significantly more medical conditions as compared to others without a history of mental health disorders. This is not to suggest the presence of a mental health disorder(s) predisposes a person to a life of chronic pain following adulthood injury requiring emergent care. While it is acknowledged that the Emergency Department environment presents a challenge, if not a trigger, to both busy, time-strapped, clinicians, and the patients themselves, knowledge of pre-existing diatheses could inform and streamline new clinical pathways for acute MSK injury on a patient-by-patient basis. The case of a Caucasian woman in her twenties seeking repeated ED management over a 7 year period is used to highlight the challenges for both the patient and the healthcare providers in, and beyond, the ED. CASE PRESENTATION The repeated voluntary ED presentations (38 visits over 7 years, from January 2015 – February 2021) were observed to be for persistent musculoskeletal pain, involving an extremity and upper limb pain. Pre-existing diagnoses of Mood Disorder, Depression, and an Eating Disorder (Anorexia Nervosa) were recorded at each ED presentation of persistent MSK pain involving an extremity, and while considered, did not feature in the clinical work-up. The retrospective record review was approved by the Northern Sydney Local Health District Human Research Ethics Committee, ethics approval number – 2021/STE02301: SSA. Design Retrospective interrogation of electronic medical records obtained from January 2015 until July 2021 capturing relevant data for acute presentations of MSK pain intersecting with mental health admissions over the preceding 12-month periods at a district hospital Emergency Department. Setting Emergency department triage facility for a large urban district hospital serving a catchment of over 1.5 million people. Subject A case report of an individual in their twenties, with multiple ED presentations (38 visits) over a 7 year period, classified by the treating ED physician/ clinicians using the SNOMED CT system at each presentation. The SNOMED CT is defined as a standardised, multilingual vocabulary of clinical terminology containing more than 300,000 medical concepts used by health care providers within the electronic exchange of clinical health information (10, 11) . The SNOMED CT is made up of the numerical codes, known as concepts, used to identifying clinical information. The number of concepts used are largely if not completely dependent on the clinical setting and patient census. In this case, the number of concepts available in a busy urban ED with level 1 trauma status is in the thousands. The concepts are divided into different groups such as body structure, clinical findings, geography, location and biological products represented by different concepts based on the complexity of the presenting condition. The terminology classifies presentations under findings, disorders, diagnoses and similar with individual numbers. SNOMED CT classifies “findings” as observations which may be objective or subjective information from a primary source, including human observation whereas the term “disorder” refers to as an abnormal clinical state and are classified under the hierarchy of disease (10). SNOMED CT however also tends to be subjective and have the same description while referring to different concepts due to the ambiguity dependant on the triage (12). The ED admission data captured the date, the patient’s reason for the visit to ED, MSK diagnosis provided at triage, and the pre-existing MH diagnosis. Under SNOMED CT, findings refer to observations that exist at the time of recording, while disorder suggests an abnormal and underlying psycho-physical pathological process that remains a vulnerability even post completion of treatment (11). As summarised in Table 1, the repeated MSK/ acute pain related presentations observed over the 2-year period were for persistent musculoskeletal pain involving an extremity(11). There were multiple mental health related admissions separate to the acute MSK pain presentation at ED over this period recorded initially for an unspecified mood (affective) disorder, progressing to Dysthymia/ Mood Disorder, followed by a separate admission for Post-traumatic stress disorder (PTSD), a further mental health admission for Dissociative convulsions, and the last captured admission was for Anorexia Nervosa (classified under Eating Disorder/s). Information regarding social circumstances, such as living independently or in supported accommodation, employment or education status, social supports both informal and formal including community mental health services, General Practitioner and any non-governmental organisations involvement was not available.
Title: Sirolimus-induced DRESS syndrome in a stem cell transplant patient.Authors: Fortunato CASSALIA1, Alice SPILLER1, Roberto SALMASO1, Francesca CAROPPO1,2, Anna BELLONI FORTINA1,2Affiliations:Dermatology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy.Pediatric Dermatology Unit, Department of Women and Children’s Health, University of Padua, Padua, Italy.Corresponding Author: Francesca Caroppo, MD Unit of Dermatology, Department of Medicine University of Padova, Italy Via Vincenzo Gallucci 4, 35121, Padova, Italy e-mail: email@example.comKeywords:Word count: 1329Tables: NoneFigure: 3References: 9Conflicts of interest: NoneAcknowledgements: NoneAuthor Contributions: All authors contributed to designing and conducting the work, drafting, and revising the manuscript and approved the final version for submission.ABSTRACTBACKGROUND: We present a case of sirolimus-induced DRESS syndrome in a stem cell transplant patient. Sirolimus is an immunosuppressive drug that inhibits the mTOR pathway. It is commonly used in organ transplants to prevent rejection. While no sirolimus-induced DRESS cases have been reported, allergic reactions with everolimus, a similar drug, have been documented. DRESS syndrome is a severe drug reaction characterized by fever, rash, and organ involvement. Diagnosis is based on clinical findings and laboratory tests. Early recognition, discontinuation of the drug, and supportive care are crucial in managing DRESS syndrome, often involving systemic corticosteroids.CASE REPORT A 24-year-old man who had undergone haplo-TESE transplantation for acute lymphatic leukaemia presented with diffuse itchy eczematous lesions. Initially diagnosed as atopic dermatitis, he received topical steroid therapy and NB-UVB phototherapy, but his condition worsened. Two months later, he returned to the emergency department with eczematous patches, xerosis, fever, chills, and generalized edema. His medical history included relapses of leukaemia, acute cutaneous graft-versus-host disease (GVHD), and Evans syndrome. He had been on sirolimus immunosuppressive therapy before the onset of symptoms. A skin biopsy revealed spongiotic dermatitis with dermal eosinophils, suggestive of drug reaction or atopic reaction. Based on the severity of the symptoms and histological findings, the patient was diagnosed with sirolimus-induced DRESS syndrome. Sirolimus was discontinued, and oral steroid therapy was initiated, leading to significant improvement. At the one-month follow-up, the patient was symptom-free and had lost the gained weight.CONCLUSION Although no cases of sirolimus-induced DRESS syndrome have been reported, allergic reactions with eosinophilia induced by everolimus have been documented. And since sirolimus and everolimus, both mTOR inhibitors, share a common mechanism of action, therapeutic indications, pharmacokinetics, adverse effects and drug interactions, it cannot be ruled out that sirolimus may trigger DRESS syndrome in patients with risk factors. In our case, the patient’s history characterized by stem cell transplantation and multiple immunosuppressive therapies may have contributed to the development of DRESS syndrome after beginning sirolimus therapy. This case may be the first evidence of sirolimus-induced DRESS syndrome in a stem cell transplant patient and highlights how early diagnosis, discontinuation of the culprit drug and appropriate management are crucial for a favourable outcome.BACKGROUND We present a case of sirolimus-induced DRESS syndrome1in a stem cell transplant patient. Sirolimus, also known as rapamycin, is an immunosuppressive and antiproliferative drug that inhibits the mammalian target of rapamycin (mTOR) pathway2. It has a wide range of clinical applications and has been extensively studied in various fields of medicine. Sirolimus is commonly used in solid organ transplants to prevent acute rejection and improve transplant survival with the advantage of reducing the nephrotoxicity associated with calcineurin inhibitors3. Although no cases of sirolimus-induced DRESS syndrome have been reported, allergic reactions with eosinophilia induced by everolimus, a similar drug of the mTOR inhibitor family, have been documented. In particular, cases of drug reaction with eosinophilia and systemic symptoms (DRESS) caused by an everolimus-eluting stent have been reported4. DRESS syndrome, also known as drug-induced hypersensitivity syndrome (DIHS), is a severe adverse drug reaction characterized by fever, skin rash, multi-organ involvement and eosinophilia. The pathogenesis of the DRESS syndrome remains unclear, involving a complex interaction between drug metabolism, immune dysregulation and genetic factors. Skin manifestations vary from maculopapular eruptions to severe exfoliative dermatitis, while organ involvement often involves the liver, kidneys, lungs and haematological system. Other systemic symptoms may include lymphadenopathy, myocarditis and interstitial nephritis. The diagnosis of DRESS syndrome is based on the recently validated RegiSCAR score5 which considers clinical findings, temporal relationship with drug exposure and blood tests. Early recognition and discontinuation of the involved drug are crucial for the management of DRESS syndrome. Supportive care and careful monitoring of organ function are essential, while symptomatic treatment aims to improve symptoms. Systemic corticosteroids are often administered to suppress the immune response6.CASE REPORTA 24-year-old boy, who had previously undergone haplo-TESE transplantation (transplantation of haploidentical haematopoietic stem cells for acute lymphatic leukaemia, presented to the dermatology outpatient clinic for the onset of a diffuse eruption with itchy eczematous lesions. The initial clinical presentation was diagnosed as atopic dermatitis and topical steroid therapy was recommended. In the following days, due to the lack of clinical response and the worsening of the skin eruption, about two months later the patient returned to the emergency department complaining of diffuse xerosis mixed with eczematous, itchy, finely scaling patches. In addition, the patient complained of fever and chills and significant and consistent oedema all over his body. He also reported a weight gain of 9 kg in the last month and eosinophilia >20% with leukopenia (Figure 1). The medical history revealed that the patient was diagnosed with acute lymphatic leukaemia in 2003 and underwent treatment according to the AIEOP LLA 2000 protocol (Prednisone, Vincristine, Daunorubicin, L-asparaginase, methotrexate, 6-Mercaptopurine, Cyclophosphamide, Cytarabine, Dexamethasone). In 2015, the patient developed a relapse for which he was treated according to the AIEOP protocol BFM 2009 concluded in 2017 (Prednisone, Vincristine, Daunorubicin, L-asparaginase, methotrexate, 6-Mercaptopurine, Cyclophosphamide, Cytarabine, Dexamethasone). However, in 2018, the patient developed a new relapse and therefore underwent haplo-TESE stem cell transplantation. Unfortunately, in 2019, the patient suffered an acute cutaneous GVHD for which he underwent treatment with oral cyclosporine in combination with tacrolimus that led to a rapid improvement of the skin manifestations. Unfortunately, in 2020 he was diagnosed with Evans syndrome and was treated with oral steroids; once the acute phase was over, the patient started immunosuppressive therapy with sirolimus 2 mg/die. Given the history and the severity of the clinical picture, the patient was hospitalized and a skin biopsy with histological examination was performed. The result of the histological examination revealed a hyperkeratosis with focally confluent spongiosis and irregular acanthosis of the epidermide. The underlying superficial dermis shows a modest infiltrate of lymphocytes, plasma cells and eosinophils, the latter also observed in the deep dermis. Specific histochemical stains did not reveal the presence of mucins and fungi (Alcial Blue and PAS) while immunohistochemical reactions for T and B lymphocytes excluded the clinical hypothesis of GVHD. The morphological picture depicts a spongiotic dermatitis with a discrete presence of dermal eosinophils suggesting the possibility of drug reaction vs. atopic reaction (Figure 2). Considering the clinical picture and the histological examination, the diagnosis of DRESS syndrome induced by sirolimus was made7. The drug was withdrawn and scaled-up oral steroid therapy was instituted, after 3 weeks of therapy the patient ceased taking the oral steroid. At the follow-up visit after one month the oedema was in remission, the patient no longer complained of any symptoms and had lost the previously accumulated kg (Figure 3).DISCUSSION The case described presents a 24-year-old boy with a complex medical history, including a previous diagnosis of acute lymphatic leukaemia and subsequent relapses, which required intensive treatments such as stem cell transplantation and immunosuppressive therapy. The patient presented to the dermatology outpatient clinic with diffuse itchy eczematous lesions, initially diagnosed as atopic dermatitis. Despite topical steroid therapy, the patient’s condition worsened with dry, itchy patches mixed with xerosis concomitant with fever, swelling, weight gain and abnormal blood results. Skin biopsy ruled out the diagnosis of graft-versus-host disease (GVHD). Based on the clinical presentation, histological findings and history of sirolimus therapy, the diagnosis of sirolimus-induced DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome was made. Sirolimus was discontinued and the patient started oral steroid therapy, which was gradually reduced and finally discontinued. After three weeks of treatment, the patient’s symptoms improved, including remission of oedema, and at the one-month follow-up visit the patient was asymptomatic and had lost the weight gained during the illness. DRESS syndrome is a severe form of drug reaction in which skin manifestations and systemic involvement are associated. The onset time is usually longer than in other delayed skin reactions, on average 6-8 weeks after the introduction of the responsible drug. It is a severe idiosyncratic T-cell mediated reaction, classified as a type Vb and sometimes IVc delayed hypersensitivity reaction. DRESS is presumed to result from a complex interaction between drug exposure (such as vaccines or biological drugs), genetic predisposition and/or viral reactivation, and the development of this serious clinical condition would appear to be the result of the cumulative effect of aligned risks1. Early recognition and discontinuation of the culprit drug are crucial for the management of DRESS syndrome. Systemic corticosteroids are often used to suppress the inflammatory response and supportive care is provided for any organ involvement6. Although no cases of sirolimus-induced DRESS syndrome are reported in the literature, allergic reactions with eosinophilia induced by everolimus have been described. In particular, cases of drug reaction with eosinophilia and systemic symptom syndrome caused by an everolimus-eluting stent have been reported4. Sirolimus and everolimus both belong to the class of drugs called mTOR inhibitors and share several features8, including: (1) Mechanism of action: Sirolimus and everolimus act by inhibiting the mammalian target of rapamycin (mTOR); (2) therapeutic indications: both are used in immunosuppressive therapy to prevent organ rejection in transplant patients. (3) Pharmacokinetics: both are administered orally and are rapidly absorbed. They have a large volume of distribution and are extensively metabolised in the liver. (4) Adverse effects: They have common adverse effects including immunosuppression, which may increase the risk of infection, delay wound healing and altered response to vaccines. Other potential side effects include hyperlipidaemia (elevated blood lipid levels), peripheral oedema, gastrointestinal disorders, and metabolic abnormalities; (5) drug interactions: both drugs are metabolised by cytochrome P450 enzymes, which may lead to potential drug interactions with other drugs that act on these enzymes9. It is important to consider these interactions when prescribing or administering these drugs. In our case, the patient’s history of previous intensive treatments, stem cell transplantation and immunosuppressive therapies may have contributed to immune system dysregulation and the onset of DRESS syndrome following the initiation of sirolimus therapy. Timely diagnosis, discontinuation of the drug and appropriate management led to the resolution of symptoms and general improvement of the patient’s condition. The case emphasizes the importance of careful monitoring and consideration of potential adverse drug reactions in patients undergoing complex treatment regimes. This case could be the first evidence of DRESS syndrome induced by sirolimus in a stem cell transplant patient.FIGURE 1 Eczematous, itchy, finely scaling patches and significant and consistent oedema.FIGURE 2 Flap of skin with hyperkeratosis, focally confluent spongiosis and irregular acanthosis of the epider-mide. Modest infiltrate of lymphocytes, plasma cells and eosinophils, in the deep dermis.FIGURE 3 One month after withdrawal of SirolimusREFERENCESRamirez, G. A., Ripa, M., Burastero, S., et al . (2023). Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Focus on the Pathophysiological and Diagnostic Role of Viruses. 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