Three cases of Nattrassia mangiferae (Scytalidium dimidiatum) infection in Singapore.

To determine if there is a difference in early relapse rates and adrenal suppression between patients receiving an 8-day course of 40 mg/day prednisolone and those receiving an 8-day tapering course of prednisolone. This was a prospective, randomized, open clinical trial conducted in a tertiary care center. All asthmatic patients with exacerbation who were judged well enough for discharge home from the emergency department were eligible for participation. Patients with a history of chronic obstructive pulmonary disease, congestive heart failure, pneumonia, pneumothorax, or other pulmonary process and asthmatics already using inhaled or oral steroids within 2 weeks of admission to the emergency department were excluded. Patients on discharge were administered either on 8-day course of 40 mg/day prednisolone or an 8-day tapering course of prednisolone (tapering from 40 mg to 0 mg). Patients were asked to return on Day 12 for cosyntropin stimulated test and pulmonary function testing and on Day 21 for pulmonary function testing only. A group of 13 patients treated with non-tapering course (40 mg/day) of prednisolone for 8 days were compared to a group of 13 patients treated with a tapering course (40 mg taper by 5 mg/day) for 8 days. There were no differences in the FEV1 percent predicted (Days 12 and 21), the incidence of relapse, or the incidence of adrenal suppression between the 2 groups. In this small study, we found no significant difference in relapse rate or adrenal suppression between asthmatics receiving an 8-day tapering dose of prednisolone and those receiving 40 mg/day prednisolone upon discharge from the emergency department.

Introduction Gout is a very common inflammatory arthritis caused by the deposition of monosodium urate crystals in the joint, which is normally managed by urate-lowering therapy like allopurinol or febuxostat. A major therapeutic challenge is refractory gout, especially in older patients who have renal impairment, gastrointestinal sensitivity, and cardiovascular disease. This case is particularly challenging due to the elderly patient having multiple comorbidities and drug intolerances, which highlights the limitations of conventional therapy and the need to consider biologic agents for difficult-to-treat cases. Case description We report the case of a 70-year-old gentleman referred to the rheumatology clinic for management of refractory gouty arthritis. The patient had a history of intolerance to standard urate-lowering therapies, including allopurinol and colchicine, both of which caused severe diarrhoea. His extensive comorbidities included type 2 diabetes mellitus, ischaemic heart disease (status post-CABG and stenting), hypertension, hyperlipidaemia, osteoporosis, heart failure, irritable bowel syndrome, and a prior stroke. Following a recent myocardial infarction, he developed multiple gout flares during his hospital stay and was treated with prednisolone 40 mg, resulting in symptomatic improvement. However, he declined benzbromarone initially. At a routine two-year follow-up, he was tried on probenecid, which resulted in a severe itchy rash over the bilateral lower limbs. A subsequent trial of benzbromarone again led to severe diarrhoea. Sulfinpyrazone was also attempted but resulted in similar gastrointestinal intolerance. His serum uric acid remained elevated at 516 µmol/L. Allopurinol was cautiously reintroduced, along with low-dose prednisolone (5 mg), but he continued to experience diarrhoea and frequent flareups affecting the knees, ankles, hands, and shoulders. He required intermittent courses of prednisolone (up to 30 mg), which he tapered but was unable to discontinue completely due to recurrent attacks. He then had a fall and sustained a vertebra fracture. Three months later, he still reports two additional flares managed with a tapering course of prednisolone. Examination revealed ankle tenderness without active synovitis; serum urate remained elevated at 489 µmol/L. Due to the patient’s refractory disease and treatment intolerance, biologic therapies such as anakinra or rasburicase were considered. Tragically, before these could be initiated, the patient suffered a right thalamic haemorrhage and passed away several months later. This case highlights the significant management challenges in treating refractory gout in patients with multiple comorbidities and limited pharmacological options. Discussion Gout is a treatable inflammatory arthritis caused by urate crystal deposition in joints. The long-term management of gout involves urate-lowering therapy with a xanthine oxidase inhibitor, allopurinol, or febuxostat. This patient poses a clinical challenge as he develops gastrointestinal manifestations with the first-line treatment allopurinol and colchicine. Given his multiple comorbidities, non-steroidal agents would be risky, and he was intolerant to colchicine too, leaving only steroids as options for flares. Febuxostat was not initiated due to ischaemic heart disease. The second challenge arises when he develops a cutaneous reaction to probenecid, followed by a gastrointestinal reaction to benzbromarone and sulfinpyrazone. Despite a cautious rechallenge with allopurinol, the patient was still unable to tolerate it. Interleukin-1 inhibitor may be considered for this patient. However, this treatment might not be feasible for a frail elderly patient with multiple comorbidities. The limited therapeutic option in this patient led to steroid dependence, which led to vertebra fractures and frequent gouty flares. This case demonstrates the need for early identification of treatment intolerance, close monitoring of urate levels, and a tailored approach. Unfortunately, before advanced therapies could be initiated, the patient suffered a fatal thalamic haemorrhage—likely influenced by underlying vascular disease and prolonged steroid exposure. Key learning points Management of gout can be challenging, especially in patients with multiple comorbidities and intolerant to first-line treatment. Steroid-dependent individuals demonstrate poor disease control and can lead to multiple complications, including fractures and cardiovascular risk. A personalised, multidisciplinary approach is very crucial for managing complex gout cases, especially for elderly patients with polypharmacy.

Introduction Longitudinally extensive transverse myelitis (LETM) in children raises concerns for serious underlying autoimmune conditions. Neuromyelitis optica spectrum disorder (NMOSD), often associated with anti-aquaporin-4 (AQP4) antibodies, can present with LETM and is increasingly recognised in paediatric populations. Juvenile systemic lupus erythematosus (jSLE) may manifest with central nervous system involvement, including myelitis. While NMOSD and SLE can occur independently, their coexistence—especially at initial presentation—is rare and diagnostically challenging. We report a paediatric case of LETM that led to the simultaneous diagnosis of NMOSD and jSLE, highlighting the importance of early recognition, comprehensive autoimmune evaluation and multidisciplinary collaboration. Case description An 8-year-old girl presented on Christmas evening with sudden bilateral leg numbness, difficulty standing, back pain, and urinary retention. Her history was otherwise unremarkable, aside from an innocuous fall 10 days earlier. Prior to admission, she developed thoracic and lumbar back pain and constipation over four days. Examination revealed lower limb weakness (power 4/5), brisk reflexes, abdominal tenderness, and a sensory level at T9/T10, but no rash, fever or optic neuritis on ophthalmic evaluation. She had thromboyctopaenia (platelet count nadir of 42) and lymphopenia. MRI scan of the spine showed long-segment spinal cord dilation suggestive of transverse myelitis. She was treated with 5 days of IV methylprednisolone, which led to partial and comparatively quick improvements in her mobility. She was discharged on a tapering course of prednisolone commencing at 40 mg with a plan to wean over the course of 5 weeks and twice daily intermittent catheterization. Three weeks later, she was readmitted with fever and signs suggestive of meningoencephalitis; her inflammatory markers were elevated, and she responded to antibiotics and antiviral therapy with all cultures (urine, blood, CSF) and CSF PCRs negative. Serum and CSF aquaporin-4 antibody positivity supported a diagnosis of NMOSD, while her ANA and dsDNA positivity indicated systemic lupus erythematosus (SLE). There was no evidence of other systemic involvement, and repeat MRI showed near complete resolution of inflammation. There were no significant neurological sequelae aside from ongoing twice daily CIC, gait was normal though running was still impaired. This child met criteria for SLE and NMOSD which can co-exist with lupus. Discussion This case underscores the importance of recognizing autoimmune overlaps in children presenting with transverse myelitis, particularly when associated with positive autoantibodies. Autoantibodies associated with SLE and Sjogrens have been associated with CNS AQP4 antibodies. In these patients NMOSD can precede or follow their rheumatological diagnosis. The coexistence of SLE and NMOSD influences management and prognosis, requiring a multidisciplinary approach to optimize outcomes and prevent future relapses or neurological sequelae. There was input from tertiary and quaternary neurology teams as well as rheumatology, neurology, urology and radiology teams. Discussions considered whether all features present at diagnosis could be explained by just one or the other diagnosis. It was felt that both were co-existing, and the NMOSD was distinct from neuropsychiatric SLE with the presence of LETM driven by AQP4 antibodies. She met SLICC and 2019 ACR criteria for SLE though mainly immunological and haematological domains (strongly positive ANA and dsDNA, thrombocytopaenia, leucopaenia and positive DCT). Given the associated risk of recurrent CNS inflammation with AQP4 antibodies present the aim was to prevent further flares and following discussions with a specialist neurologist in neuroinflammation alongside local rheumatology and neurology she was commenced on MMF as maintenance therapy. A longer weaning course of prednisolone was also prescribed. She still undergoes regular reviews and remains a positive and stoic character. Her physical function has recovered however her bladder residual volume is still significant to require CIC. She has recently had an admission for a urinary tract infection as a complication of this. Key learning points • Consider autoimmune rheumatological diseases in cases of NMOSD and vice versa - the overlap is documented and has consequences for prognosis and treatment. • Management of these complex cases is multi-disciplinary, treatment should be guided by all specialties involved and specialist advice sought as needed. • NMOSD associated with autoimmune disease is considered more severe with more frequent relapses and worse prognosis, our case highlights an example of early intervention where prompt treatment with IV steroids and early initiation of DMARD have so far provided rapid initial recovery and a period of relative stability. • Trasnverse myelitis can be one of the neurological presentations of jSLE, which can be clinically, radiologically and immunologically differentiated from coexisting NMOSD, which has implications on planning the treatment too. • Although reported in adults, coexistence of jSLE and NMOSD is exceedingly rare, limited to a handful of case reports.

Double-blind trial of steroid tapering in acute asthma

Stable Elevations in FIX Activity and Reductions in Annualized Bleeding Rate over up to 2 Years of Follow-up of Adults with Severe or Moderate-Severe Hemophilia B Treated with AMT-060 (AAV5-hFIX) Gene Therapy

Two-Year Combination Antibiotic Therapy With Clarithromycin, Rifabutin, and Clofazimine for Crohn’s Disease

Introduction Dermatomyositis is a rare autoimmune muscle disease that presents commonly in the fourth decade with symmetrical proximal muscle weakness and findings of Göttron’s papules, Göttron’s sign or heliotrope rash. Variants such as clinical amyopathic dermatomyositis (CADM) exist in 5-20% of patients with dermatomyositis, involving dermatological manifestations without symmetrical muscle weakness. However, limitations in the diagnostic criteria pertaining to cutaneous findings have been identified in existing literature. Our case presents a patient with an initial diagnosis of CADM in view of meeting the diagnostic criteria. Upon further thorough clinical examination and a skin biopsy, he was revealed to have psoriasis instead. Case description We present a 44-year-old gentleman with a background of amyopathic dermatomyositis and Type I Von Willebrand’s disease. He has no family history of autoimmune disorders nor psoriasis. He initially presented a decade ago with fatigue, myalgia and swollen joints limiting daily tasks. He had a rash over the extensor surfaces of his hands, thought to be Göttron’s papules, with further rash over knees and feet. There was no proximal weakness. Positive tests included anti-nuclear antibodies (ANA) and anti Ro-60. Based on the rash and clinical synovitis, he was diagnosed with amyopathic dermatomyositis. He was commenced on methotrexate and a 6-months tapering course of prednisolone which improved his rash and joint pain. Unfortunately, he was lost to follow-up two years later and was not on treatment since. Seven years later, the GP referred to Rheumatology detailing similar symptoms occurring for a year – erythematous itchy rash over dorsal aspects of his hands, elbows, knees, metatarsals and scalp with associated arthralgia, sicca symptoms and intermittent exertional breathlessness. He had a rash over his eyebrows, sparing the eyelids. Erythematous plaques with silvery scales and dystrophic toenails were noted. There was no alopecia, photosensitivity, mucosal ulcers, dysphagia, proximal weakness, peripheral oedema, nor systemic symptoms. Lung fields were clear. He was tested positive for ANA, anti Ro-60, Ro-52, PmScl-75 and PmScl-100 antibodies. Anti double-stranded DNA, complement, RF, Anti-CCP, CK, immunoglobulins, uric acid, CRP and ESR were normal. CT chest/abdomen/pelvis (CAP), XR hands and feet, MRI thighs, ultrasound salivary glands and lung function tests were normal. Ultrasound of his right hand showed synovitis over multiple joints without hyperaemia nor erosion. The dermatologists then performed a punch biopsy, which showed psoriasis. The clinical impression of his recent presentation likely suggests undifferentiated connective tissue disease. Given arthralgia, sicca symptoms, ongoing skin psoriasis and positive antibodies, methotrexate was restarted. Discussion The initial diagnosis of amyopathic dermatomyositis was made following the combination of plaque-like rash in an area associated with Gottren’s Papules (extensor surfaces of hands) with autoantibodies consistent with dermatomyositis. Absence of muscle involvement is unusual, but not unheard of, and initial treatment followed established guidelines for treatment of amyopathic dermatomyositis. The rash improved, appearing to further support the initial diagnosis. On return of symptoms, the patient was reviewed by a different rheumatologist, who noted that the rash had features not entirely consistent with Gottren’s papules, thus prompting the dermatology referral, and subsequent diagnosis. Methotrexate and prednisolone are effective treatments for both dermatomyositis and psoriasis, and as such, the treatment for the amended diagnosis of psoriasis mirrored the treatment initially given. This case highlights the importance of challenging previously established diagnoses if the presentation does not follow a classic pattern. In this case, the diagnosis of amyopathic dermatomyositis has a predicted incidence of less than 1 in 100,000, while psoriasis has an incidence of approximately 3%, making it by far a more likely pathology. It is also an important reminder that response to immunosuppressant medication is not in itself a confirmation of diagnosis, and that medication wherever possible should be commenced only when a diagnosis is confirmed. In this case, the patient received treatment which was safe and effective for his underlying condition. However, patients are at risk of receiving unnecessary, ineffective and sometimes potentially hazardous treatments as a consequence of misdiagnosis. Key learning points It is important to exclude common diagnoses which can mimic a rare condition, prior to initiating treatment. In assessment of rashes, all areas of the body should be examined, and dermatology advice and biopsy sought in cases of clinical uncertainty or potentially rare diagnoses. Concurrent discovery of clinical signs and serological markers can often support a diagnosis, but the entire clinical picture should be considered. Immunosuppressant medications such as steroids and methotrexate have a wide range of uses, and response to these medications does not always indicate the correct diagnosis. In some conditions, incorrect use of medications can mask the underlying diagnosis to sometimes dangerous effect.

BackgroundSirolimus is a non-calcineurin immunosuppressant commonly used in patients with organ transplantation to prevent rejection. While various inflammatory syndromes have been described post-sirolimus use, it is uncommon to have inflammatory...

Adenocarcinoma of the lung is the most common type of lung cancer and is classified as one of the non-small cell lung cancers. It typically arises in the peripheral regions of the lungs, affecting the dense glandular tissues. Most patients diagnosed with pulmonary adenocarcinoma are current or former smokers and present with nonspecific respiratory symptoms such as a persistent cough and shortness of breath. Many also go on to develop B symptoms, including weight loss and night sweats.We present a case of an 84-year-old Caucasian woman, a lifelong nonsmoker and teetotaller, who presented with a two-week history of dry cough, shortness of breath, and chest heaviness following receipt of her influenza vaccination. Her past medical history included hypertension (treated with amlodipine and perindopril), glaucoma, and bilateral cataracts. Initial blood tests showed normal infection and inflammatory markers. However, her chest X-ray was suggestive of pulmonary fibrosis, with fibrotic changes predominantly in the bilateral lower lung zones. She was initially treated with a tapering course of prednisolone for suspected hypersensitivity pneumonitis. Lung function tests were arranged, and a computed tomography chest scan revealed tiny centrilobular nodules in both lungs, located in peribronchovascular, perifissural, and subpleural areas. Further history revealed regular exposure to a Western Rosella bird. She denied dampness, mold, or known asbestos exposure at home. Connective tissue disease screening and avian precipitins, however, were negative.She later presented again with worsening symptoms. Arterial blood gas analysis revealed type 1 respiratory failure. The patient was admitted to the intensive care unit and was intubated and ventilated. A repeat chest X-ray showed progressive parenchymal changes without regression. Intravenous 500 mg of methylprednisolone was started; however, she showed no improvement with it. The patient's case was discussed at the lung multidisciplinary team meeting, and a lung biopsy was recommended, which was carried out via bronchoscopy. Histopathology revealed fragmented cores of adenocarcinoma with lepidic and papillary growth patterns, mucinous type, consistent with a primary lung origin (T4N0M1a). The patient’s condition continued to deteriorate despite intensive care support, and she sadly passed away two weeks after admission.This case underscores the need to maintain a broad differential diagnosis, particularly in patients who fail to improve with treatment. It also emphasizes the role of biopsy in resolving the diagnostic challenge, as imaging studies did not provide a clear diagnosis.

IntroductionSarcoidosis affects approximately 1% of the population. There are two situations where it came become life threatening: seizures secondary to neuro-sarcoidosis and arrhythmias due to cardiac infiltration. Currently there are limited licenced therapies for the treatment of sarcoidosis. We describe a case of cutaneous and neuro-sarcoidosis who developed subsequent multi-system sarcoidosis.Case descriptionA previously fit and well 50-year-old presented to his local hospital with tonic clonic seizures. He worked as a mortgage broker and never smoked. There was no pro-drome and on examination it was noted he had erythema nodosum on his shins. He was investigated with a CT head and subsequent MRI demonstrating enhancement of his leptomeninges, mid brain parenchyma, hypothalamus and pituitary gland. A lumbar puncture was performed with an elevated protein level of 934g with a normal glucose and lymphocyte level. The CSF was negative for TB. A CT of his chest was performed demonstrating bilateral hilar lymphadenopathy and subsequent histology of these lymph nodes demonstrated non-necrotising, non-caseating epithelioid granulomas. A diagnosis of sarcoidosis was made and he was commenced on mycophenolate. His disease remained quiescent for 5 years before the eruption of further skin lesions. He developed multiple subdermal nodules on his fingers, wrists, elbows which were biopsied demonstrating cutaneous sarcoidosis. Neurological examination demonstrated brisk lower limb reflexes with upgoing plantars. He was commenced on a tapering course of prednisolone and an evaluation for extra-cutaneous disease was made. An IL2Ra was 4719ng/L (423-1843) with a normal ACE. Pituitary axis testing revealed a slightly raised prolactin (326 mIU/L). A CT-PET was performed demonstrating extensive metabolic activity in his skin, central nervous system, liver, spleen, salivary glands, skeletal uptake in both humeral heads alongside myocardial uptake. An urgent cardiac MRI was performed demonstrating active myocardial disease. An ECG did not demonstrate any conduction abnormalities. A diagnosis of multi-system sarcoidosis was made warranting an urgent MDT discussion given the progression of his disease.DiscussionIn this particular case, it had been assumed that his sarcoidosis was inactive until the emergence of the skin lesions. It was the skin lesions that lead to an assessment for multi-system sarcoidosis. It is common for the serum ACE level to be normal, as seen in up to 50% of cases and it was the Il2Ra elevation that prompted the CT-PET request. Given the extent and progression of disease despite treatment with mycophenolate, this gentlemen was given a tapering regime of prednisolone (starting at 20mg) and his mycophenolate was switched to methotrexate which has shown to have superior efficacy to mycophenolate for sarcoidosis. Furthermore, infliximab at a dose of 5mg/kg was commenced shortly after to control the increasing CNS lesions. Infliximab is a well recognised treatment for sarcoidosis; however, due to limited clinical trial data, it remains unlicenced for use in sarcoidosis with the exception of neuro-sarcoidosis (following the failure of DMARD therapy). To date, the patient remains well with no further worsening in his disease.Key learning pointsSarcoidosis is a clinical entity with no one specific test. The diagnosis should be constructed using multiple parameters including radiographic findings, biochemical and histological proof. We advocate that suspected cases of sarcoidosis should have a thorough assessment and discussion in the MDT. When isolated skin disease is suspected or confirmed, baseline testing for extra-cutaneous involvement should be sent including NT-proBNP, troponin I and T, creatinine kinase, a full pituitary profile, ACE and cytokine assessment for Il2Ra, amongst other routine blood tests. An ECG is of paramount importance as arrhythmias are common cardiac features of sarcoidosis. Should there be ongoing suspicion of multiple organ involvement, a CT-PET should be performed at baseline. Isolated lymph node disease does not commonly warrant treatment; however, this cohort of patients should be closely monitored. The management of sarcoidosis in the acute setting is commonly prednisolone, but steroid sparing therapies should be considered in patients needing recurrent, prolonged courses of corticosteroids or those with evidence of critical organ involvement such as CNS, cardiac or lung disease. Life threatening disease or disease refractory to DMARD therapy should be considered for anti-TNF therapy with infliximab or adalimumab. More recently, tofacitinib has been promising as a treatment for sarcoidosis with clinical trials in Yale and Portland. Newer therapies in development include the GM-CSF inhibitor namilumab, and efzofitimod, a neuropilin 2 inhibitor.

BackgroundKimura’s disease is a rare chronic inflammatory disorder of unknown etiology that is seen in people of Asian descent. It is characterized by head and neck subcutaneous nodules along with lymphadenopathy, which is usually solitary but can be generalized. It is diagnosed histopathologically by the proliferation of blood vessels and germinal centers in lymphoid follicles, along with variable degrees of fibrosis and extensive eosinophil infiltration. Its localized form is treated with surgical excision, while generalized lesions and those that do not respond to surgical excision can be managed with steroids or radiotherapy.CaseIn this report, we present the first case of Kimura’s disease in the Ethiopian literature in a 40-year-old Ethiopian man that presented with generalized pruritic subcutaneous nodules and lymphadenopathy, which were effectively managed with a tapering course of prednisolone, and a relapse that showed good sustained response with slow steroid taper.ConclusionWe have demonstrated that, even though it is very rare in the African continent, Kimura’s disease is to be considered as a differential diagnosis for patients that present with subcutaneous nodules and lymphadenopathy. We also have demonstrated that relapses can be effectively managed with reinitiation of the same dose of steroids but with a very slow taper.

This paper describes the clinical, laboratory and histological findings in three horses with immune-mediated polysynovitis; they had lost weight, suffered intermittent fever, were lethargic and stiff, and had effusions in...

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon disorder marked by severe immune system dysfunction and excessive inflammation. Its clinical features often mimic those of severe sepsis, including persistent high fevers, multiorgan failure, cytopenia, and coagulation abnormalities. HLH can be triggered by infections, malignancies, rheumatological disorders, genetic factors, and medications, particularly those that cause immunosuppression. Ocrelizumab, an anti-CD20 monoclonal antibody used in the treatment of multiple sclerosis, has been associated with rare immune-mediated complications. In this case, the patient presented with generalized fatigue, fever, and neutropenia and was initially treated for neutropenic sepsis. Despite standard antibiotic therapy, there was no clinical improvement. A CT scan of the chest, abdomen, and pelvis revealed multiple lung nodules with surrounding ground-glass halos, suggestive of an invasive fungal infection, along with hepatosplenomegaly, raising concern for an underlying hematological malignancy. The patient was managed with intravenous antibiotics and antifungal therapy. However, due to persistent high fevers, markedly elevated ferritin levels (peaking at 20,695 ng/mL), and pancytopenia, an H-score for HLH was calculated, yielding a score of 302, indicating a greater than 99% probability of the condition. Based on these findings, intravenous anakinra (100 mg) was initiated. A bone marrow biopsy showed features suggestive of HLH but no evidence of hematological malignancy. The case was discussed at the HLH multidisciplinary team meeting with the HLH team at University College London Hospitals NHS Foundation Trust, and methylprednisolone (500 mg) was subsequently started. Consultations with the rheumatology and respiratory teams were also arranged. The patient's condition gradually improved, and she was discharged on Day 31 with a tapering course of prednisolone, continued oral antifungal therapy, and a follow-up PET scan scheduled. This case highlights the importance of recognizing HLH as a potential complication in patients receiving immunosuppressive therapies such as ocrelizumab. Prompt diagnosis and aggressive management are critical for improving outcomes and preventing further complications.

An Unexplained Lesion on the Leg of a 2-year-old Girl.

An 85-year-old man presented with a 1 month history of jerks affecting his trunk and lower limbs. He reported severe subacute low back pain and gradually progressive weakness in both...