Initiation Of Steroid Treatment Research Articles

Case Report : Nephrotic Syndrome

Nephrotic syndrome (NS) is characterized by persistent heavy proteinuria (mainly albuminuria) (>2 g/m2/24 hours); hypoproteinemia (serum albumin 250 mg/dL); and edema. Small amounts of protein are found in the urine of healthy children. Nephrotic syndrome is an important chronic disease in children. The estimated annual incidence of nephrotic syndrome in healthy children is two to seven new cases per 100,000 children under 18 years of age. A case has been reported of a boy aged 9 years 5 months who was brought by his parents to the emergency room at Tengku Rafi'an Siak District Hospital with complaints of swelling since 2 days ago before being admitted to the hospital. Complaints accompanied by puffy eyes when waking up, urinating a little, stomach and legs feeling like they are getting bigger. History of the same complaint (+), diagnosed with nephrotic syndrome in February 2024. Children with first clinical manifestations of SN should be hospitalized in order to accelerate examination and evaluation of dietary management, edema management, initiation of steroid treatment, and parental education.

External Validation of a Urinary Biomarker Risk Score for the Prediction of Steroid Responsiveness in Adults With Nephrotic Syndrome

In idiopathic nephrotic syndrome, response to corticosteroids remains the best indicator of prognosis. Noninvasive markers to predict a patient's response to steroids would allow improved prognostication and a more personalized approach to management. We have previously derived a urinary biomarker risk score which can differentiate steroid sensitive nephrotic syndrome (SSNS) from steroid resistant nephrotic syndrome (SRNS) in children. The goal of this study was to validate this previously derived biomarker risk score in a cohort of steroid-naïve adult patients, to determine whether the panel could be used to predict steroid responsiveness at the time of initial diagnosis. In this external validation study, clinical data, and urinary specimens (obtained before initiation of steroid treatment) from adult patients were used in the Nephrotic Syndrome Study Network (NEPTUNE) cohort. A panel of 5 previously identified and validated urinary biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), vitamin D binding protein (VDBP), Fetuin-A (FetA), Transthyretin (TTR), and alpha-1 acid glycoprotein 2 (AGP2) was measured. A summary risk score for steroid resistance was calculated based on biomarker concentrations. Receiver operating characteristic curves were created for each log-transformed biomarker concentration and for the individual and combined biomarker risk score. The urine biomarker risk score predicted development of steroid resistance, with optimal sensitivity and specificity of 0.74, and area under the receiver operating characteristic curve (AUC) of 0.79 using both absolute and creatinine-corrected concentrations. This study validates the previously derived urinary biomarker risk score to predict steroid resistance in adult patients with nephrotic syndrome at initial diagnosis.

Case Report of a Severe Presentation of Anti-Contactin-1 Nodopathy

A 46-year-old, previously healthy woman presented via telemedicine with 14 months of progressive asymmetrical weakness, numbness, paresthesias and tremors. History and clinical exam findings suggested a peripheral etiology resembling a variant CIDP presentation. Electrodiagnostic testing identified only one motor nerve with signs of demyelination; the remainder of motor and sensory nerves were unable to be evoked. MRI showed diffuse enhancement of the trigeminal nerve and cauda equina. CSF revealed albuminocytologic dissociation. The patient was treated empirically with methylprednisolone for a clinically suspected variant of CIDP, more specifically a nodo-paranodopathy. Two weeks after initiation of steroid treatment, cerebrospinal fluid and serum yielded antibodies to contactin-1 which coincided with our clinical suspicion for an autoimmune nodo-paranodopathy, which is known to be refractory to IVIG. Rituximab was added given the patient’s severe presentation at the time of diagnosis. The autoimmune nodo-paranodopathies are treatable, even in the case of a severe presentation. Lack of clinician awareness and delay in diagnosis can be detrimental as in the case of our nearly paralyzed patient. It is important to raise awareness of the disease, its presentation and therapeutic management since early diagnosis and correct treatment is paramount for neurological recovery.

A rare presentation of neurosarcoidosis as the superior orbital fissure syndrome

We are reporting a rare case of neurosarcoidosis that presented with superior orbital fissure syndrome. A 51-year-old Indian woman who suffered from 2 weeks duration, insidious onset gradually progressive left sided headache limited to forehead, left periorbital pain, diplopia on looking toward left, and numbness on the left forehead was referred to our hospital. Ophthalmic findings included left oculomotor nerve, trochlear nerve and abducens nerve palsies, absent corneal reflex, and loss of touch, pain and temperature sensation in V1 distribution. Brain and orbit magnetic resonance imaging (MRI) showed contrast enhancing area at the left orbital apex with normal optic nerve. Normal CSF analysis. High ESR, and chest x-ray showing non-homogenous patchy opacities in bilateral lung fields leaded us for neoplastic screening. Chest computed tomography (CT) revealed multiple ill-defined irregular lung parenchymal nodular opacities of varying sizes involving bilateral lungs with enlarged mediastinal and bilateral axillary lymph nodes. Elevated angiotensin converting enzyme level was found. Biopsy of the axillary lymph node showed non-caseating granulomatous lymphadenitis with giant cells containing schaumann bodies and asteroid bodies in the cytoplasm. These findings indicating an inflammatory response induced by sarcoidosis. After the initiation of steroid treatment, the patient experienced complete remission without any recurrence. When examining a case presenting with superior orbital fissure syndrome with contrast enhancing MRI lesion at the orbital apex, the additional chest CT to exclude neoplastic lesions can detect pulmonary sarcoidosis and extraneural lesions. These may avoid delays in the diagnosis and management of neurosarcoidosis.

Long-term (16–26 years) follow-up outcome of steroid therapy in refractory autoimmune sensorineural hearing loss

Autoimmune sensorineural hearing loss (ASHL) is a rare disease of uncertain etiology, with no established treatment strategy. The duration of morbidity is increased in refractory cases; and therefore, the preservation of hearing and the prevention of adverse effects with steroid therapy are serious long term issues to consider. Long-term follow up of patients treated for ASHL was performed retrospectively in order to elucidate the pathogenesis of ASHL, evaluate the consequences of steroid therapy, and determine a promising treatment course. The cohort in this study consists of four female patients with refractory ASHL that were followed for 16–26 years. Three patients already had profound deafness on one side, probably due to ASHL, before the initiation of steroid treatment. ASHL was managed with steroid administration and the hearing was evaluated through regular audiometric tests (173–212 times). The relationship between pure tone threshold average and steroid dose was reviewed over a long-term follow-up period for each patient. During follow-up, hearing deficit progressed rapidly several times in all patients, as did responsiveness to steroid therapy. Long-term high-dose steroid therapy was not required for hearing maintenance. Hearing thresholds were nearly maintained in three patients during the 16- to 21- year follow-up, and gradually declined over a 26-year follow-up period in one patient. Considering the progress due to presbycusis, the maintenance of hearing was considered sufficient in all patients. No serious adverse effects were observed in any of the patients. Management of patients affected by ASHL with regular audiometry allowed for hearing maintenance without the morbidity of prolonged steroid therapy. The current observations give insight into the pathogenesis of ASHL pathogenesis and establish an efficient course of treatment.

Glucocorticoid effects on bone strength in children with renal diseases.

Glucocorticoids (GC) are essential medicines for idiopathic steroid-sensitive nephrotic syndrome (ISSNS) and IgA nephropathy (IgAN), with good clinical results. However, they cause bone fragility. The aim of this study was to elucidate GC effects on bone strength assessed as bone mineral density (BMD) and bone quality, using bone turnover markers (BTM), in children with ISSNS or IgAN. Eleven children with ISSNS and 13 with IgAN were included. All the patients received GC treatment according to each protocol. The BMD and BTM-serum alkaline phosphatase (S-ALP), tartrate-resistant acid phosphatase 5b (S-TRACP-5b), and undercarboxylated osteocalcin (S-ucOC)-were measured from the initiation of steroid treatment (STx) to the end of STx in both groups. In ISSNS, S-ALP and S-ucOC levels were decreased significantly at 1 month. BMD and S-TRACP-5b levels showed no significant change through this observation period. In IgAN, BMD and S-ALP levels were decreased significantly at 1 and 3 months, respectively, and recovered to baseline at 10 months after the initiation of GC dosage reduction. S-TRACP-5b levels were decreased significantly at 3 months and remained lower than at baseline through the observation period. In both groups, S-ucOC levels did not directly reflect bone strength. This study clarified the following three points regarding GC effects on bone strength in children with ISSNS or IgAN: first, S-ALP is a more sensitive bone quality marker than S-TRACP-5b; second, BMD loss was observed only when both S-ALP and S-TRACP-5b levels decreased, and third, S-ucOC levels do not directly reflect bone strength.

Development of interstitial pneumonia during treatment with eribulin: a case report

BackgroundEribulin is typically used to treat patients with advanced breast cancer, and anti-cancer agents often cause the development of interstitial pneumonia in Japanese patients with advanced cancer. However, few case reports have addressed eribulin-induced interstitial pneumonia. Herein, we report a rare case of interstitial pneumonia—specifically, organized pneumonia—during treatment with eribulin in a patient with advanced breast cancer.Case presentationA 52-year-old Japanese woman was diagnosed as having advanced breast cancer 3 years before the admission described in the present report. She had received eribulin as third-line chemotherapy. Five days after her second treatment with eribulin, she was admitted to our hospital with dyspnea and dry cough. Upon admission, a chest computed tomography scan showed consolidation, with air bronchograms along the bronchovascular bundle of both lower lobes. The patient’s serum levels of sialylated carbohydrate antigen Krebs von den Lungen-6 were high, as were her surfactant protein-D levels. There was no evidence of heart failure, renal failure, or infection. Based on the clinical cause, as well as on the findings of organized pneumonia, the patient was diagnosed as having interstitial pneumonia and treated with corticosteroids. After the initiation of steroid treatment, her respiratory condition and chest radiological findings improved.ConclusionsThis case reveals an association between eribulin treatment and interstitial pneumonia. To our knowledge, this is the first case report to describe eribulin-induced organized pneumonia. Clinicians should be aware that interstitial pneumonia can develop during treatment with anti-cancer agents.

The Effects of Glucocorticoids on Bone Strength in Children with Renal Diseases

Background: We evaluated the effect of glucocorticoids (GCs) on bone strength via bone mineral density (BMD) scores and serum alkaline phosphatase (S-ALP) levels in children with idiopathic steroid-sensitive nephrotic syndrome (ISSNS) or IgA nephropathy (IgAN). Methods: Sixteen children with ISSNS and 13 with IgAN were eligible for this study. The BMD and S-ALP levels were measured before the initiation of steroid treatment (STx), one month after initiation of STx and one month after terminating STx (Phases 0, 1 and 2). For IgAN, scores and levels were measured before the initiation of STx (Phase 0) and 1, 3, 6, and 12 months after the initiation of STx (Phases 1, 2, 3, and 4). Results: In ISSNS, the BMD and S-ALP levels were significantly lower in Phase 1 than in Phase 0; however, scores and levels returned to baseline in Phase 2. In IgAN, BMD was significantly lower in Phase 2 than in Phase 0 while S-ALP levels were significantly lower in Phases 1, 2, and 3 compared to Phase 0. No significant difference was observed between Phase 0 and Phase 4. Conclusions: In ISSNS, bone strength recovered one month after terminating STx. In IgAN, bone strength recovered 10 months after tapering of STx.

Intravascular Large B-Cell Lymphoma Mimicking Central Nervous System Vasculitis

Intravascular large B-cell lymphoma (IVBCL) represents a rare subtype of extranodal diffuse large B-cell lymphoma characterized by selective growth of neoplastic cells within the lumen of small and medium-sized vessels. The clinical spectrum is heterogeneous dominated by neurological and skin manifestations. Intra-vitam diagnosis still remains challenging and usually requires brain biopsy since no pathognomonic neuroradiological findings do exist for IVBCL. We report on the case of a 65-year old male patient presenting with multifocal neurological signs and symptoms including cognitive deficits, aphasia and paraparesis as leading features. Imaging findings were suggestive for cerebral vasculitis prompting initiation of steroid treatment. After initial stabilization the patient deteriorated in spite of systemic steroid treatment, developed severe sepsis and finally died from multi-organ failure. Histopathological findings revealed CD20 positive lymphoma cells in small- and middle-sized vessels of the cerebrum, the lungs and the skin diagnostic for IVBCL. This case should raise the alertness for consideration of IVBCL as a differential diagnosis resulting in early brain biopsy, if no etiology for CNS vasculitis is evident.

Comparison of Outcomes in Patients With Probable Versus Definite Cardiac Sarcoidosis

Patients with probable cardiac sarcoidosis (CS) who satisfy only clinical cardiac findings for CS are not uncommon. The aim of this study was to compare outcomes between patients with probable CS and those with definite CS treated with steroids. The study population consisted of 101 consecutive patients who satisfied clinical cardiac findings for CS. Patients with definite CS were defined as having histologic or clinical confirmation of CS according to the guidelines and were treated with steroids. Patients with probable CS were defined as having only clinical cardiac findings but not definite CS because of no histologic confirmation or extracardiac sarcoidosis and were not treated with steroids. The end point was major adverse cardiac events. Forty-seven patients had definite CS, and the other 54 had probable CS. Except for serum angiotensin-converting enzyme levels and left ventricular dysfunction, clinical characteristics were similar between the 2 groups. Over a median follow-up period of 15 months, major adverse cardiac events occurred more frequently in patients with probable CS than in those with definite CS (74% vs 53%, p=0.029). The event-free survival rate was worse in patients with probable CS than in those with definite CS (log-rank test, p=0.006). Cox proportional-hazards analysis showed that probable CS was an independent predictor of major adverse cardiac events. In conclusion, outcomes were worse in patients with probable CS than in those with definite CS treated with steroids. The initiation of steroid treatment may be considered for patients who satisfy only clinical cardiac findings for CS.

Magnetic Resonance Imaging Characteristics of Tumefactive Demyelinating Lesions

Tumefactive demyelinating lesions (TDLs) are often misdiagnosed as brain tumors. To identify imaging characteristics of TDLs for their proper diagnosis, their differences from malignant gliomas, etc., were investigated based on 3-Tesla magnetic resonance imaging (MRI) and MR spectroscopy data that was obtained from 5 patients diagnosed with TDLs in our hospital. MfRI displayed a paraventricular lesion with a maximum diameter of ≥2 cm. Diffusion-weighted imaging (DWI) displayed a region of bright signal intensity at the margin of the lesion, and apparent diffusion coefficient (ADC) imaging displayed high signal intensity at the core of the lesion. The mass effect was mild relative to the size of the lesion, and the edema around the lesion was mild to moderate. Gadolinium-enhanced MRI displayed a characteristic open-ring sign, in which the ring of enhancement was incomplete (open towards the cortex), with the medullary vein running through the lesion, resulting in the enhancement of the surrounding area. MR spectroscopy displayed an increase in the choline peak, a decrease in the N-acetyl aspartate (NAA) peak, the presence of lactate/lipid peaks, and the presence of β, γ-glutamate-glutamine (GLX) peaks that are slightly shifted to a higher resonance frequency (2.1 - 2.4 ppm) from the NAA peak. Taken together, the following main characteristics were identified as imaging features of TDLs: bright rim on DWI, a high signal core on ADC imaging, an open-ring sign, and β, γ-GLX peaks on proton MR spectroscopy. We concluded that the key to the improvement of neurological symptoms of patients is the prompt initiation of steroid treatment following the accurate diagnosis of TDLs.

Outcomes in Patients With High-Degree Atrioventricular Block as the Initial Manifestation of Cardiac Sarcoidosis

Although high-degree atrioventricular block (AVB) is a common initial manifestation of cardiac sarcoidosis, little is known about the outcomes. The aim of this study was to assess outcomes in patients with AVB as an initial manifestation of cardiac sarcoidosis compared with those in patients with ventricular tachyarrhythmia (VT) and/or heart failure (HF). Fifty-three consecutive patients with cardiac sarcoidosis, who had high-degree AVB (n = 22) or VT and/or HF (n = 31), were enrolled. The end point was defined as major adverse cardiac events, including cardiac death, ventricular fibrillation, sustained VT, and hospitalization for HF. Over a median follow-up period of 34 months, the outcomes of major adverse cardiac events were better in patients with high-degree AVB than in those with VT and/or HF (log-rank test, p = 0.046). However, this difference was due mainly to HF hospitalization. The outcomes of fatal cardiac events, including cardiac death, ventricular fibrillation, and sustained VT, were comparable between the 2 groups (log-rank test, p = 0.877). The fatal cardiac events in patients with high-degree AVB were not associated with the initiation of steroid treatment or left ventricular dysfunction. In conclusion, the outcomes of major adverse cardiac events are better in patients with high-degree AVB than in those with VT and/or HF. However, patients with high-degree AVB have a high rate of fatal cardiac events, similar to those with VT and/or HF. An indication for an implantable cardioverter-defibrillator, but not a pacemaker system, can be considered in patients with cardiac sarcoidosis manifested by high-degree AVB.

Cronkhite–Canada Syndrome Diagnosis in the Absence of Gastrointestinal Polyps

A 66-year-old male patient presented with nausea, abdominal pain, occasional rectal bleeding, progressive dysgeusia, onicodystrophy, and alopecia. Endoscopic exam and biopsies revealed severe atrophy and diffuse marked edema of mucosa of stomach and duodenum. No evidence of polyps was found in any portion of the gastrointestinal tract. The diagnosis of Cronkhite-Canada syndrome (CCS) was rendered. The patient symptoms resolved completely after initiation of steroid treatment. This additional case of CCS illustrates how the diagnosis of CCS does not require the presence of polyps but is defined by the appreciation of the diffuse marked edema and atrophy of the gastrointestinal mucosa.

Problem-based review: The Patient with Acute Adrenal Failure

Acute adrenal crisis is an important condition to consider in any shocked patient presenting to the acute medical unit. This article aims to highlight the key aspects of initial management, focussing on the importance of rapid recognition and prompt initiation of steroid treatment.

Acute Q Fever Presenting as Antiphospholipid Syndrome, Pneumonia, and Acalculous Cholecystitis and Masquerading as <i>Mycoplasma pneumoniae</i> and Hepatitis C Viral Infections

We report a case of Q fever-related antiphospholipid syndrome in a patient presenting with acalculous cholecystitis and pneumonia. Serial laboratory tests indicated that the previous serological tests suggesting hepatitis C virus and Mycoplasma pneumoniae infections were false-positives. The patient's fever persisted despite treatment with doxycycline, but disappeared 1 day after initiation of steroid treatment. To avoid incorrect diagnosis and subsequent delays in appropriate treatment of Q fever patients, the possibility that Q fever can masquerade as other infections or as an autoimmune disease should be kept in mind.

Incidence of Adrenal Insufficiency and Impact of Corticosteroid Supplementation in Critically Ill Children with Systemic Inflammatory Syndrome and Vasopressor-Dependent Shock: Hebbar KB, Stockwell JA, Leong T, Fortenberry JD. Crit Care Med 2011;39:1145–50.

The importance of diagnosing adrenal insufficiency in pediatric patients with the Systemic Inflammatory Response Syndrome (SIRS) has not been validated, nor has the subsequent treatment with corticosteroids. This study was a retrospective review of 78 patients with a median age of 84 months, who were treated at the Atlanta Pediatric Intensive Care Unit (PICU) with a protocol for steroid supplementation in patients meeting SIRS criteria. The primary outcome was decrease in vasopressor requirements after initiation of steroid treatment. All PICU patients requiring intravenous fluids and vasopressors for treatment of shock were tested for adrenal insufficiency with a standardized corticotrophin stimulation test. Patients were then classified as having absolute adrenal insufficiency (AAI) if a basal cortisol level < 18 mg/dL was measured vs. relative adrenal insufficiency (RAI) if the corticotrophin stimulation test induced a change in measured cortisol levels. Of the initial 78 patients, 44 (56%) had AAI and 39 (50%) had RAI, for a total of 69 (88%) with some degree of adrenal dysfunction. These patients were then treated with weight-based doses of hydrocortisone, with the addition of enteral 9-alpha-fludricortisone at the discretion of the treating physician. A diagnosis of AAI was shown to be associated with increased patient age, higher incidence of Staphylococcus aureus bacteremia, increased mechanical ventilation requirements, and higher vasopressor requirements. A statistically significant decrease in duration of vasopressor use was found in those treated with steroids. Dopamine use decreased from 24 h to 8 h (p < 0.01), norepinephrine from 27.5 h to 8 h, (p = 0.0001). There was no difference found between steroids being initiated before or after 12 h of vasopressor initiation. Overall, 98% (43/44) of patients with AAI and 92% (36/39) with RAI showed a > 50% reduction in vasopressor dosage within 4 h of initiating corticosteroids. Importantly, the study found no incidence of catheter-associated bloodstream infections, ventilator-associated pneumonias, gastric bleeding, or critical illness myopathy/polyneuropathy, some of the often-reported side effects of steroids, although 14 patients (18%) had rebound hypotension after steroid discontinuation requiring additional fluid boluses. Mortality was very low in the entire cohort (5%), so comparisons could not be made between the groups.

A Retrospective Comparison of Health Care Outcomes in Crohnʼs Disease Patients with and without Prolonged Steroid Monotherapy

Purpose: Short-term steroid use is effective in improving Crohn's disease (CD) symptoms; however, lack of effectiveness and increased health risks make long term steroid use undesirable.1 Methods: To assess effects of prolonged steroid monotherapy on indicators of flares (hospitalization/surgery/emergency dept [ED]) and occurrence of osteoporosis in patients with CD, a retrospective analysis of a Thomson MarketScan® claims database (Q1 2000-Q4 2009) was performed. MarketScan included combined claims of approximately 100 employers and covered >60 million lives across all census regions. CD patients >18 years old with ≥2 CD diagnoses (ICD-9-CM: 555.xx) receiving oral or intravenous steroids without concurrent immunomodulators or biologics were grouped into 2 mutually exclusive cohorts: prolonged steroid monotherapy (≥3 months) or no prolonged steroid monotherapy (<3 months). Beginning at initiation of steroid treatment (index date), 1-year outcomes, which included CD-related resource utilization and complications related to steroid use, were assessed. Study outcomes were compared between cohorts using multivariate logistic regressions adjusting for demographics, comorbidities, prior treatments, and baseline health care resource utilization. Results: 64.6% of the 11,124 patients included in the study had prolonged use of steroids as monotherapy. During the 1 year evaluation period, patients with CD with prolonged steroid monotherapy had higher risks of experiencing CDrelated inpatient visits and other study events compared with those with no prolonged steroid monotherapy (Table).Table: No Caption available.Conclusion: Based on this claims data analysis, the majority of patients with CD received prolonged steroid monotherapy, which was associated with greater risks of CD-related hospitalization, ED visits, and osteoporosis compared with short-term steroid monotherapy.

Glucocorticoids as a novel approach to the treatment of disabling side effects of sodium stibogluconate

Intravenous sodium stibogluconate (SbV) is the mainstay of treatment for mucocutaneous leishmaniasis. Incidence of this disease is increasing in the UK, partly because of returning military personnel. SbV has a side effect profile that requires treatment interruption in up to 28% of patients. Side effects can be unpleasant and - in the case of QTc prolongation - dangerous. A volunteer medical worker returning from Guatemala was diagnosed with mucocutaneous leishmaniasis. Because of previous renal problems, NSAIDs were contraindicated. Severe side effects of myalgia and arthralgia would have necessitated a treatment interruption, but a trial of prednisolone gave excellent symptomatic relief. The patient's QTc, amylase and C-reactive protein also fell following initiation of steroid treatment. The SbV treatment course was completed successfully. This is the first reported case of the dangerous and disabling side effects of SbV being treated very effectively with glucocorticoids. Of note is the normalization of the apparently sodium stibogluconate-induced prolongation of the QTc interval. Further investigation into this potential beneficial effect is warranted.

All-transretinoic Acid (ATRA) Treatment-related Pancarditis and Severe Pulmonary Edema in a Child With Acute Promyelocytic Leukemia

Use of all-transretinoic acid (ATRA) with other chemotherapeutic agents in the treatment of acute promyelocytic leukemia (APL) has been shown to cause the differentiation of abnormally granulated specific blast cells into mature granulocytes by acting on the t(15; 17) fusion gene product. The complete remission rate is increased and survival time is prolonged in APL patients who receive chemotherapy plus ATRA, whereas ATRA syndrome and other ATRA-related adverse effects including pseudo tumor cerebri, headache, severe bone pain, mucosal and skin dryness, hypercholesterolemia, and cheilitis may be observed especially during induction phase of the treatment. In this paper, we report a 9-year-old girl with APL who developed pancarditis while receiving the APL-93 treatment protocol. In our patient, endocarditis and myocarditis were initially determined after ATRA treatment during the induction part of the protocol. All findings disappeared after ATRA was discontinued. When ATRA was readministered in the maintenance part of the treatment protocol, she developed pancarditis and severe pulmonary edema. As her symptoms decreased dramatically with the discontinuation of ATRA and the initiation of steroid treatment, the clinical picture strongly suggested the ATRA treatment as the causative factor. To the best of our knowledge, this clinical picture of pancarditis secondary to ATRA treatment has not been reported earlier in the English literature.

Corticosteroids Correct Aberrant CFTR Localization in the Duct and Regenerate Acinar Cells in Autoimmune Pancreatitis

Corticosteroids are now widely accepted as a treatment for autoimmune pancreatitis (AIP). However, the molecular mechanism by which steroid treatment improves AIP remains largely unknown. The aim of this study was to elucidate cellular mechanisms by which corticosteroids improve both pancreatic exocrine function and histopathology in AIP. Pancreatic exocrine function was evaluated by the secretin-stimulated function test and pancreatic biopsy specimens were processed for histologic analysis at the time of diagnosis and 3 months after initiation of steroid treatment. Expression and localization of proteins was assayed by immunohistochemistry. Analysis of immunoglobulin (Ig)G4-positive plasma cells was used to verify inflammation in AIP. The number of IgG4-positive plasma cells in pancreatic sections was decreased by steroid treatment, indicating reduced inflammation. Fluid, bicarbonate (HCO(3)(-)), and digestive enzyme secretions all were impaired in most patients with AIP. Corticosteroids improved both HCO(3)(-) and digestive enzyme secretion. A large fraction of the cystic fibrosis transmembrane conductance regulator (CFTR), which plays a central role in pancreatic duct HCO(3)(-) secretion, was mislocalized to the cytoplasm of duct cells before treatment. Corticosteroids corrected the localization of CFTR to the apical membrane, accounting for the improved HCO(3)(-) secretion. Steroid treatment resulted in regeneration of acinar cells, accounting for restored digestive enzyme secretion. Corticosteroids reduce inflammation and restore both digestive enzyme and HCO(3)(-) secretion in patients with AIP by regenerating acinar cells and correcting CFTR localization in pancreatic duct cells. Mislocalization of CFTR may explain aberrant HCO(3)(-) secretion in other forms of pancreatitis.