Hepatomegaly and jaundice as the presenting symptoms of systemic light-chain amyloidosis: A case report

BACKGROUND Light chain(AL)amyloidosis is a plasma cell dyscrasia characterized by the pathologic production and extracellular tissue deposition of fibrillar proteins derived from immunoglobulin AL fragments secreted by a clone of plasma cells,which leads to progressive dysfunction of the affected organs.The two most commonly affected organs are the heart and kidneys,and liver is rarely the dominant affected organ with only 3.9%of cases,making them prone to misdia-gnosis and missed diagnosis.CASE SUMMARY A 65-year-old woman was admitted with a 3-mo history of progressive jaundice and marked hepatomegaly.Initially,based on enhanced computed tomography scan and angiography,Budd-Chiari syndrome was considered and balloon dilatation of significant hepatic vein stenoses was performed.However,addi-tional diagnostic procedures,including liver biopsy and bone marrow-exami-nation,revealed immunoglobulin kapa AL amyloidosis with extensive liver involvement and hepatic vascular compression.The disease course was progre-ssive and fatal,and the patient eventually died 5 mo after initial presentation of symptoms.CONCLUSION AL amyloidosis with isolated liver involvement is very rare,and can be easily misdiagnosed as a vascular disease.

Successful treatment of lichen amyloidosis coexisting with atopic dermatitis by dupilumab:Four case reports

BACKGROUND Lichen amyloidosis(LA)is a chronic,severely pruritic skin disease,which is the most common form of primary cutaneous amyloidosis.The treatment of LA has been considered to be difficult.LA may be associated with atopic dermatitis(AD),and in this setting,the treatment options may be more limited.Herein,we report four cases of LA associated with AD successfully treated by dupilumab.CASE SUMMARY In this article,we describe four cases of patients who presented with recurrent skin rash accompanied by severe generalized intractable pruritus,diagnosed with refractory LA coexisting with chronic AD.Previous treatments had not produced any apparent improvement.Thus,we administered dupilumab injection subcutaneously at a dose of 600 mg for the first time and 300 mg every 2 wk thereafter.Their lesions all markedly improved.CONCLUSION Dupilumab may be a new useful treatment for LA coexisting with AD.

Dupilumab for treatment of severe atopic dermatitis accompanied by lichenoid amyloidosis in adults:Two case reports

BACKGROUND Lichenoid amyloidosis(LA)is a subtype of primary cutaneous amyloidosis characterized by persistent multiple groups of hyperkeratotic papules,usually on the lower leg,back,forearm,or thigh.LA may be associated with several skin diseases,including atopic dermatitis(AD).The treatment of LA is considered to be difficult.However,as there is some overlap in the etiopathogenesis of LA and AD,AD treatment may also be effective for LA.CASE SUMMARY Case 1:A 70-year-old man was diagnosed with severe AD with LA based on large dark erythema and papules on the trunk and buttocks and dense hemispherical millet-shaped papules with pruritus on the extensor side of the lower limbs.He had a long history of the disease(8 years),with repeated and polymorphic skin lesions.Given the poor efficacy of traditional treatments,this patient was recommended to receive dupilumab treatment.At the initial stage,300 mg was injected subcutaneously every 2 wk.After 28 wk,the drug interval was extended to 1 mo due to the pandemic.Follow-up observations revealed that the patient reached an Eczema Area Severity Index of 90(skin lesions improved by 90%compared with the baseline)by the end of the study.Moreover,Investigator's Global Assessment score was 1,and scoring atopic dermatitis index and numeric rating scale improved by 97.7%and 87.5%compared with the baseline,respectively,with LA skin lesions having largely subsided.Case 2:A 30-year-old woman was diagnosed with severe AD with LA,due to dense and substantial papules on the dorsal hands similar to changes in cutaneous amyloidosis,and erythema and papules scattered on limbs and trunk with pruritus,present for 25 years.After 16 wk of dupilumab treatment,she stopped,and skin lesions completely subsided,without recurrence since the last follow-up.CONCLUSION Dupilumab shows rational efficacy and safety in the treatment of severe AD with LA,in addition to benefits in the quality of life of the patients.

Rare manifestation of familial vitreous amyloidosis caused by Gly103Arg transthyretin

AIM:To identify and analyze the genotype of the patients with special ocular manifestations of familial vitreous amyloidosis(FVA)in a Chinese Han family.METHODS:Pars plana vitrectomy(PPV)surgery was performed on a 52-year-old Chinese woman presented with vitreous amyloidosis and progressive visual impairment,without evidence of cardiac,renal,gastrointestinal,central nervous system or peripheral nervous system dysfunction.During the surgery,the patient presented with a gray-white dense and thick cotton woollike change in the vitreous body,accompanied by complete retinal detachment.Additionally,hard,free and movable yellow-white deposits were observed in the posterior pole and surrounding retina,the vitreous and subretinal deposits were examined by Congo red staining and immunohistochemical pathological examination,and whole exome sequencing was performed on blood samples from the patient and her cousin.RESULTS:During the operation,it was discovered that there was a complete detachment of the retina and a significant amount of hard,free-floating yellow-white deposits were observed beneath the posterior pole and surrounding retina.This is an exceedingly rare ocular manifestation.Pathological examination of the vitreous and subretinal deposit specimens revealed positive Congo red staining,as well as elevated vascular endothelial growth factor(VEGF)expression in vascular endothelial cells within the sediment specimens upon immunohistochemical examination.The patient and her cousin both exhibited a heterozygous mutation in Glyl03Arg within the transthyretin(TTR)gene,resulting in a substitution of glycine(Gly)at position 103 with arginine(Arg).CONCLUSION:FVA may present with various ocular manifestations,but panretinal detachment is a rare occurrence.In cases where retinal detachment persists for an extended period of time,amyloid deposits may form under the retina through retinal tears,leading to subretinal deposits that can impede retinal reattachment and negatively impact visual prognosis.Elevated levels of VEGF in the eyes of FVA patients may indicate an overexpression state,necessitating careful postoperative follow-up.The heterozygous mutation Gly103Arg may represent a unique pathogenic site in Chinese individuals.

Cardiac amyloidosis presenting as pulmonary arterial hypertension:A case report

BACKGROUND Pulmonary hypertension is a rare cardiopulmonary disease,with an insidious onset that usually worsens rapidly.Amyloid light chain(AL)amyloidosis is a rare systemic disease caused by extracellular deposition of pathologic,insoluble,and proteinaceous fibrils in organs and tissues;however,it is difficult to diagnose given its varied and nonspecific symptoms.To date,rare cases of amyloidosis with pulmonary hypertension have been reported.Of note,the optimal treatments for cardiac amyloidosis complicated with pulmonary hypertension remain unclear.CASE SUMMARY We report a case of a 51-year-old woman who presented with progressively worsening dyspnea.Transthoracic echocardiography indicated severe pulmonary hypertension.Twenty-seven months after first admission,the patient returned with symptoms of progressive heart failure.A myocardial tissue sample stained with Congo red was positive,and the patient was ultimately diagnosed with AL amyloidosis with cardiac involvement.CONCLUSION Although pulmonary hypertension may be idiopathic,it is frequently associated with other conditions.In rare cases,pulmonary hypertension can be a complication of AL amyloidosis,which should be seriously considered in any adult presenting with nonspecific signs or symptoms of cardiac distress.

Membranous nephropathy with systemic light-chain amyloidosis of remission after rituximab therapy:A case report

BACKGROUND About 70%-80%of patients with primary membranous nephropathy(MN)have phospholipase A2 receptor(PLA2R)in renal tissue.Systemic light-chain(AL)amyloidosis is the most common type of amyloidosis.MN complicated with amyloidosis is rare.CASE SUMMARY A 48-year-old Chinese male presented with nephrotic syndrome,positive serum PLA2R antibody,and positive serum and urine IgG-lambda type M-protein,with a normal ratio of serum-free light-chain level.The patient was diagnosed with MN accompanied by AL amyloidosis.He was treated with rituximab with glucocorticoids and CyBorD regimen of chemotherapy.After 21 mo of follow-up,the patient achieved complete remission regarding nephrotic syndrome without adverse effects of chemotherapy.CONCLUSION We report a case of PLA2R-related MN complicated with primary AL amyloidosis only with renal involvement and successfully treated with rituximab,glucocorticoids and chemotherapy.

ABCB4 gene mutation-associated cirrhosis with systemic amyloidosis:A case report

BACKGROUND Gene mutations in ATP-binding cassette,subfamily B(ABCB4)lead to autosomal recessive disorders.Primary light amyloidosis is a rare and incurable disease.Here,we report a rare case of liver cirrhosis caused by ABCB4 gene mutation combined with primary light amyloidosis.CASE SUMMARY We report a case of a 25-year-old female who was hospitalized due to recurrent abdominal pain caused by calculous cholecystitis and underwent cholecystectomy.Pathological examination of the liver tissue suggested liver cirrhosis with bile duct injury.Exon analyses of the whole genome from the patient’s peripheral blood revealed the presence of a heterozygous mutation in the ABCB4 gene.Bone marrow biopsy tissues,renal puncture examination,and liver mass spectrometry confirmed the diagnosis of a rare progressive familial intrahepatic cholestasis type 3 with systemic light chain type κ amyloidosis,which resulted in cirrhosis.Ursodeoxycholic acid and the cluster of differentiation 38 monoclonal antibody daretozumab were administered for treatment.Following treatment,the patient demonstrated significant improvement.Urinary protein became negative,peripheral blood-free light chain and urine-free light chain levels returned to normal,and the electrocardiogram showed no abnormalities.Additionally,the patient’s lower limb numbness resolved,and her condition remained stable.CONCLUSION This report presents the diagnosis and treatment of liver cirrhosis,a rare disease that is easily misdiagnosed or missed.

Screening for Transthyretin Cardiac Amyloidosis in Patients with Bilateral Carpal Tunnel Syndrome: Identifying Missed Opportunities for Early Detection and Treatment

Purpose: Transthyretin cardiac amyloidosis (ATTR-CA) has been linked to many extra-cardiac manifestations including bilateral carpal tunnel syndrome (CTS). The aim of this study is to analyze patients with bilateral CTS to identify patients with high-risk features or “red flags” for ATTR-CA, identify if systematic screening was done for ATTR-CA and define opportunities for improved detection. Methods: Out of >5000 patients with bilateral CTS evaluated in a single tertiary care center in Southeast Michigan (2010-2016), we retrospectively studied a focused population of patients: men > 50 years and women > 60 years old with bilateral CTS and atrial fibrillation (n = 295). Baseline demographic, comorbidities, and electrocardiographic and echocardiographic findings were analyzed. A high-risk group suspicious for ATTR-CA was identified as patients with bilateral CTS, atrial fibrillation, and concomitant “red flags” including heart failure and left ventricular hypertrophy. Results: Out of 295 patients, 51.2% were female, 75.6% were White, and 22.4% were African American. Upon comparing the high-risk group (n = 67) with the remaining study population (n = 228), both diagnosis of ATTR-CA and mortality were higher among the high-risk group (7.5% vs 0.4% and 43.3% vs 24.6%, respectively, P = 0.003). Conclusions: A substantial number of bilateral CTS patients had additional “red flags” warranting formal evaluation for ATTR-CA;however, systematic evaluation for cardiac amyloidosis was not performed in many patients. This emphasizes that Multidisciplinary collaboration is needed to create a systematic workflow and to raise awareness amongst cardiologists and other physicians for suspecting ATTR-CA in bilateral CTS patients who have additional “red flags”.

Diagnostic and prognostic value of cardiac imaging in amyloidosis

Amyloidosis is an infiltrative disease caused by extracellular protein deposition that has accumulated a lot of scientific production in recent years.Different types of amyloidosis can affect the heart.Transthyretin amyloidosis and light chain amyloidosis are the two most common types of cardiac amyloidosis.These entities have a poor prognosis,so accurate diagnostic techniques are imperative for determining an early therapeutic approach.Recent advances in cardiac imaging and diagnostic strategies show that these tools are safe and can avoid the use of invasive diagnostic techniques to histological confirmation,such as endomyocardial biopsy.We performed a review on the diagnostic and prognostic implications of different cardiac imaging techniques in cardiac amyloidosis.We mainly focus on reviewing echocardiography,cardiac magnetic resonance,computed tomography and nuclear imaging techniques and the different safety measurements that can be done with each of them.

Primary Tracheobronchial Amyloidosis in China:Analysis of 64 Cases and A Review of Literature

Primary tracheobronchial amyloidosis (TBA) is a rare pulmonary disease.A systematic review was performed on 64 cases of primary TBA in China and progress in the diagnosis and treatment of this disease is discussed.The Chinese biological and medical databases from 1970 to 2010 were searched and 75 cases of complete clinical and pathological data were identified.The clinical characteristics of the disease were summarized and longitudinal comparisons were made of diagnostic and treatment methods over time.The results showed that the morbidity associated with primary TBA has increased over recent years.The clinical manifestations were non-specific.Progressive dyspnea, cough and sputum were the most common symptoms.The percentage of patients undergoing computed tomography (CT) scan has increased over the years.The bronchoscopy and transbrochial lung biopsy (TBLB) were usually sufficient to establish the diagnosis.Treatment was reported for a total of 44 cases.Bronchoscopic Nd:YAG laser irradiation, argon plasma coagulation (APC) and drugs administration such as steroids and colchicines were reported to be effective in some patients.It is concluded that the demographic characteristics and clinical manifestations of primary TBA patients in China are largely consistent with findings reported in other countries.Dramatically more cases were reported in recent years, mainly due to the extensive application of bronchoscopy since 1990s.Chest CT scan provides important clues for the diagnosis of the disease.The definite diagnosis was confirmed by bronchoscopic findings and Congo red staining of biopsy specimen.Bronchoscopic Nd:YAG laser irradiation, argon plasma coagulation (APC) and drugs administration, such as steroids and colchicines were reported to be effective in some patients.

Primary hepatic amyloidosis:A case report and review ofliterature

We describe a case of 42-year-old female presenting with abdominal pain associated with loss of weight and fever for 8 mo. On evaluation she had gross hepatomegaly with raised alkaline phosphatase and raised GGT levels with normal transaminases and bilirubin. On imaging she had diffuse enlargement of liver with heterogeneous contrast uptake in liver. Her viral marker and autoimmune markers were negative. Liver biopsy depicted massive deposition of amyloid in peri-sinusoidal spaces which revealed apple green birefringence on polarizing microscopy after Congo red staining. Cardiac and renal evaluation was unremarkable. Abdominal fat pad and rectum biopsy was negative for amyloid deposit. There was no evidence of primary amyloidosis as bone marrow examination was normal. Serum and urine immunofixation electrophoresis were normal. Immunoperoxidase staining for serum amyloid associated protein for secondary amyloidosis was negative from liver biopsy. We present this rare case of primary hepatic amyloidosis and review the literature regarding varied presentations of hepatic involvement in amyloidosis.

Cardiac amyloidosis: A case report and review of literature

BACKGROUND Cardiac amyloidosis,a disease caused by the precipitation of amyloid proteins in the myocardial extracellular matrix has been historically difficult to diagnose due to lack of specific clinical manifestations and necessity of biopsy to demonstrate amyloid deposition. However,advances in cardiovascular imaging techniques have facilitated earlier recognition of this disease. In addition,while once thought of as incurable,treatment strategies are emerging for cardiac amyloidosis,making early diagnosis essential.CASE SUMMARY We outline the case of a 73 years old African American female who was admitted with sudden onset shortness of breath and found to be in cardiogenic shock.Cardiac amyloidosis was suspected due to discordance between electrocardiogram and echocardiogram findings and this was subsequently confirmed with the aid of scintigraphy and an endomyocardial biopsy.CONCLUSION Our objective is to highlight the diagnostic evaluation and clinical implications of cardiac amyloidosis.

Vitrectomy for vitreous amyloidosis

AIM: To study the clinical features of vitreous amyloidosis and the effect of vitrectomy for it. METHODS: We treated 6 eyes (4 Patients) with vitreous amyloidosis from 2008 to 2009, and followed up for 18-30 months after vitrectomy. RESULTS: The visual acuity ranged from counting fingers to 3/50 before surgery and 15/50-40/50 after vitrectomy. No severe complication was observed. CONCLUSION: Vitrectomy is an effective and safe treatment for eyes with vitreous amyloidosis. A long period of follow-up after surgery should be performed.

Rare presentation of primary (AL) amyloidosis as gastrointestinal hemorrhage without systemic involvement

We are reporting a rare case of a patient with primary(AL) amyloidosis presenting with an acute non-varicealupper gastrointestinal hemorrhage in the absence ofother systemic involvement. The case report involves a58-year-old woman with significant cardiac history andhereditary blood disorder who came in complaining ofabdominal pain and coffee-ground emesis for two days.Computed tomography(CT) scan of the abdomen andpelvis with contrast revealed segmental wall thickeningof the proximal jejunum with hyperdense, heterog-enous luminal content. Similar findings were evident inthe left lower small bowel region, suspicious for smallbowel hematoma and the possibility of intraluminalclots. Esophagogastroduodenoscopy performed postresuscitation showed punctate, erythematous lesionsthroughout the stomach as well as regions of smallbowel mucosa that appeared scalloped, ulcerated, andhemorrhaged on contact. Despite initial treatment for immunostain-positive focal cytomegalovirus gastritis, follow-up esophagogastroduodenoscopy after two months continued to demonstrate friable and irregular duodenal mucosa hinting at a different underlying etiol-ogy. Pathology reports from analyses of biopsy samples highlighted infiltration and expansion of the lamina pro-pria and submucosa. Subsequent staining with congo red/crystal violet and appropriate subtyping established the diagnosis of AL(kappa)-type amyloidosis. The sig-nificance of this case lies in the fact that our patient did not have the typically seen diagnostic systemic involvements-namely of heart and kidneys-usually seen in primary(AL) amyloidosis patients. It was the persis-tent endoscopic findings and biopsy results which gave clues to the physicians regarding the possibility of an abnormal protein-deposition entity.

Digitally reinforced hematoxylin-eosin polarization technique in diagnosis of rectal amyloidosis

AIM:To investigate the efficacy of the digitally reinforced hematoxylin-eosin polarization(DRHEP)technique for detection of amyloidosis in rectal biopsies.METHODS:One hundred hematoxylin-eosin(HE)stained rectal biopsies with Congo-red(CR)-positive amyloid depositions and 50 control cases with CRnegative amyloid-mimicking areas were scanned blinded to the CR results for amyloid depositions under both bright and polarized light,and digitally photographed using the DRHEP technique,to accentuate the faint birefringence observed in HE slides under polarization.The results of DRHEP and HE evaluation were statistically correlated with CR polarization results with respect to presence and localization of amyloid deposits as well as amyloid types.RESULTS:Amyloid deposits showed yellowish-green birefringence by DRHEP,which allowed identification of amyloidosis in 41 HE-unsuspected cases(P=0.016),31 of which only had vascular deposits.True positivity was higher,and false negativity and positivity were lower by DRHEP,compared to evaluation by HE(69%,31%,and 0.8%vs 33%,67%,and 33%,respectively;P<0.0001).The sensitivity,specificity,accuracy,and positive and negative predictive values for DRHEP were69%,98%,78.6%,98.5%,and 61.25%,respectively.Reasons for DRHEP false negativity were presence of extensive background birefringence in 12 cases,absence of CR birefringent vessel in 3 cases,and missing of the tiny deposits in 9 cases,which could be improved by experience,especially in the latter case.No correlation was found between age,gender,sites of deposits,or amyloid types.CONCLUSION:The DRHEP technique improves diagnostic accuracy when used as an adjunct or a prior step to CR staining,especially for cases with limited tissues for further analysis.

Case report and review of the literature of primary gastrointestinal amyloidosis diagnosed with enteroscopy and endoscopic ultrasonography

Here, we report a rare case of primary gastrointestinal amyloidosis in a stable condition after being followed up for three years. The patient was admitted to the hospital in 2014. Tests showed decreased levels of hemoglobin and ferritin. Transoral and transanal enteroscopy showed multiple nodular protuberances in the esophagus, ileum, colon and rectum. Endoscopic ultrasonography indicated the nodular protuberances stemmed from the submucosa and partially invaded the intrinsic myometrium. Pathological examinations found multiple small nodules in the submucosa and dyed structures, which were positive for special Congo red dyeing. After treatment with oral iron supplements, the levels of hemoglobin and ferritin became normal. It is concluded that the patient represents a case of primary gastrointestinal amyloidosis with multiple nodular protuberances in the digestive tract with controllable moderate abdominal discomfort and anemia and a benign course. Enteroscopy and endoscopic ultrasonography play an important role in the diagnosis of primary gastrointestinal amyloidosis.

Rectal bleeding as a presenting symptom of AL amyloidosis and multiple myeloma

Amyloidosis of the gastrointestinal tract is a rare disease that presents with common,nonspecific signs and symptoms.It may affect any part of the gastrointestinal tract from mouth to anus.The clinical and endoscopic features are diverse and may mimic other diseases,such as inflammatory bowel disease,malignancy,ischemic colitis and,at times,collagenous colitis.We describe an uncommon case of rectal bleeding and anemia with polypoid lesions and ulcerations in the colon,as the presenting symptom of AL amyloidosis and light chain multiple myeloma.

Topical halometasone cream combined with fire needle pretreatment for treatment of primary cutaneous amyloidosis:Two case reports

BACKGROUND Primary cutaneous amyloidosis(PCA)is a chronic metabolic skin disease that has a detrimental impact on physical and mental health.It appears as mossy papules and severe itching,which is long-term and recurrent.Traditional treatments are unsatisfactory,especially for refractory cases.Fire needle therapy,which is widely used in China,has shown good clinical efficacy,as well as advantages concerning safety and cost.Clinical reports about fire needle treatment of this disease are few at present.CASE SUMMARY We report two older men who had developed maculopapules with itchiness on the trunk and arms for more than 10-15 years.Due to the dermatopathological findings,PCA was our primary consideration.They received topical halometasone cream and pretreatment with fire needle for 8-16 wk.Both patients showed significant improvement of lesions.Neither patient had recurrence with a minimum of 2 years of follow-up.CONCLUSION Topical halometasone cream and pretreatment with fire needle could be a fast,safe,and economic treatment for PCA.

Multi-modality imaging of cardiac amyloidosis: Contemporary update

Cardiac amyloidosis is a heterogeneous and challenging diagnostic disease with poor prognosis that is now being altered by introduction of new therapies.Echocardiography remains the first-line imaging tool, and when disease is suspected on echocardiography, cardiac magnetic resonance imaging and nuclear imaging play critical roles in the non-invasive diagnosis and evaluation of cardiac amyloidosis. Advances in multi-modality cardiac imaging allowing earlier diagnosis and initiation of novel therapies have significantly improved the outcomes in these patients. Cardiac imaging also plays important roles in the risk stratification of patients presenting with cardiac amyloidosis. In the current review, we provide a clinical and imaging focused update, and importantly outline the imaging protocols, diagnostic and prognostic utility of multimodality cardiac imaging in the assessment of cardiac amyloidosis.

Renal amyloidosis as a late complication of Crohn's disease:a case report and review of the literature from Japan

INTRODUCTION Secondary amyloidosis is a rare but seriouscomplication of Crohn’s disease(CD).Theincidence of the association of secondaryamyloidosis in patients with CD has been reportedto be 0.5%-8% in Western countries.However,in Japan,the number of patients with CDcomplicated by amyloidosis is limited.Thecharacteristics of their clinical manifestations andthe incidence of association are uncertain.Therefore,we report herein a patient with