Mild Normocytic Anemia Research Articles

A169 A RARE MANIFESTATION OF ENTERITIS DUE TO IMMUNE CHECKPOINT INHIBITOR: CASE REPORT OF PYLORIC STRICTURE

Abstract Background Immune checkpoint inhibitors (ICI) are immunomodulatory antibodies used to enhance the immune response against tumor cells that have revolutionized the treatment of various malignancies. ICIs pose a risk of immune-related adverse events in various organs including the gastrointestinal tract, with diarrhea and colitis being most common. ICIs can rarely cause involvement of the upper gastrointestinal tract, with case reports of gastritis, duodenitis, and esophagitis. There are very rare reports of strictures caused by ICIs, more frequently in the lower gastrointestinal tract, and only a few reports in the esophagus or duodenum. Aims We report a rare case of an upper gastrointestinal stricture due to ICI at the pylorus. Methods Case report. Results A 38-year-old woman with breast cancer on ICI pembrolizumab presented with several weeks of nausea and early satiety. She had started pembrolizumab 8 months prior, underwent neoadjuvant chemotherapy and mastectomy months ago, and completed radiation 6 weeks earlier. She also described nocturnal reflux and heartburn, but no vomiting, weight loss, or other gastrointestinal symptoms. Her examination was normal and recent bloodwork only showed a mild normocytic anemia. EGD (esophagogastroduodenoscopy) showed friable circumferential ulceration of the distal antrum with surrounding erythema and luminal narrowing from the pyloric channel to duodenum. 1-centimetre gastroscope was not passable but 4.9-millimetre pediatric gastroscope passed into the duodenum where there were no abnormalities past the duodenal bulb. Pathology showed granulation tissue, fibrinopurulent exudate, and antral mucosa with chronic active inflammation negative for Helicobacter pylori and malignancy. Oncology felt that radiation was too far from the pylorus to be responsible for the findings. High-dose proton pump inhibitor (PPI) and soft diet were recommended with minimal symptomatic improvement. 2 months later, she developed weight loss and repeat EGD showed minimal endoscopic improvement (Figure 1). ICI-related enteritis was suspected and she was started on prednisone 50 mg daily. Her appetite and nausea significantly improved. Steroid taper was planned for 8 weeks. At 3 months, symptoms recurred with prednisone taper. EGD showed only mild improvement of the duodenal stricture. Prednisone dose was increased. On repeat EGD at 7 months, the pylorus was patent with only granular inflammation predominantly in the apex of the duodenal bulb. She tolerated a slower prednisone taper thereafter. Conclusions ICI-related inflammation is common in the lower gastrointestinal tract and can less commonly affect the upper gastrointestinal tract. This is a rare report of upper gastrointestinal stricture and the first report known to us of pyloric stricture caused by ICI. Treatment may be challenging, but was achieved with PPI and high-dose steroids with slow taper. Funding Agencies None

Eculizumab Utilization in Hemolytic Uremic Syndrome (HUS) Presenting with Acute Hemolysis

Background: Hemolytic uremic syndrome (HUS) is thrombotic microangiopathy in which microthrombi are formed, consisting mainly of platelets, which will occlude the arterioles and capillaries leading to a triad of intravascular hemolysis, thrombocytopenia, and acute kidney failure. Case Presentation: A 2-year-old boy presented to our outpatient clinic with persistent diarrhea streaked with blood, vomiting, signs of dehydration, and an ingested throat. The complete blood count (CBC) revealed acute hemolysis with mild normocytic hypochromic anemia, anisopoikilocytosis, fragmented red blood cells, and moderate thrombocytopenia. The patient experienced a drastic course which was dramatically improved after the administration of eculizumab. Conclusion: Eculizumab is a recombinant humanized monoclonal antibody against complement component C5; that effectively blocks the cleavage of complement factor C5 and, subsequently, the complement membrane attacks complex C5B-9.78. While on eculizumab, our patient's kidney function improved significantly after the first dose with a creatinine of 0.56 mg/dl.

Vertebrae compression fracture due to osteonecrosis as initial sign of childhood acute lymphoblastic leukemia: A case report

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Manifestations of ALL vary from pallor, organomegaly, fever, and pancytopenia. Bone pain caused by vertebrae fracture is an uncommon manifestation of ALL, approximately only 16% of all bone pain occurrences. Fractures in ALL could occur at diagnosis and following treatment initiation. This case report described vertebrae compression fracture due to osteonecrosis as the initial sign of childhood acute lymphoblastic leukemia. CASE: An 8-year-10-month girl was referred to an orthopedic because of worsened low back pain since 1 month before, with no history of trauma. The pain was throbbing and radiated to the lower extremities. The patient was non-ambulant due to the pain. Physical examination revealed the visual analog scale was 8, tenderness in the spine, decreased strength, and range of movement in the lower extremities. There was no organomegaly in this patient. Serial laboratory examination revealed mild pancytopenia (leukopenia, mild normochromic normocytic anemia, mild thrombocytopenia) with dominancy of lymphocytes (68.1-81.9%). No blast was found in the peripheral blood smear. Magnetic Resonance Imaging of the spine revealed compression of the vertebral corpus with a pincer fracture and bone infarction. Bone marrow aspiration showed ALL-L2 with lymphoblast 50%. The patient started chemotherapy with ALL standard risk protocols and got zoledronic acid during the treatment. The patient's condition gradually improved, and able to undergo chemotherapy protocol. No side effects of zoledronic acid occurred. CONCLUSION: Vertebrae compression fracture without trauma and pancytopenia can be an early symptom of ALL. Zoledronic acid can be given concurrently with chemotherapy for bone mineralization.

Systemic-onset Juvenile Idiopathic Arthritis in a young child

We present a 31-month-old female child who was referred by the pediatricians with 1-year history of recurrent high-grade fever associated with polyarthritis and recurrent skin rash, which disappears within 24 hours of resolution of fever. She had lost the ability to walk unsupported because of persistent arthritis. Her Full Blood Count (FBC) was remarkable for marked leucocytosis, thrombocytosis, and a mild normocytic normochromic anemia; Erythrocyte Sedimentation Rate (ESR) and C-reactive Protein (CRP) were both elevated at 110mm/hour and 200mg/L (<7) respectively while serial blood cultures were negative for septicemia and blood films were negative for acute leukemia; HIV, hepatitis B and C virus, tuberculosis, rheumatic fever, rheumatoid arthritis, and connective tissue disease screenings were all negative. Her hemoglobin genotype is AA. She had repeatedly received treatments for malaria and ‘sepsis’ with parenteral and oral antimalarials and antibiotics with no permanent relief, hence the reason for referral to the rheumatologist. An assessment of Systemic-onset Juvenile Idiopathic Arthritis (SoJIA) was made when her serum ferritin came back elevated at 670ng/mL (4.63 – 204) and she was commenced on oral ibuprofen with remarkable improvement evidenced by resolution of fever, joint pain and rash and normalization of ESR, CRP and serum ferritin within 8 weeks of treatment. Although SoJIA is rare, it would be worthwhile to include this disease in the differential diagnoses and subsequent evaluation in any child presenting with unexplained recurrent fever associated with body rash and polyarthritis.

Salmonella meningitis with hydrocephalus as complication in children: A case series

Background: Bacterial meningitis by salmonella serotype is a rare infection among neonates and young children. The treatment of salmonella meningitis requires bactericidal agents that are capable of penetrating into cerebrospinal fluid (CSF). Acute complications of bacterial meningitis mainly include hydrocephalus, subdural collection, cerebral infarction, ventriculitis, empyema, intracranial abscess and cranial nerve palsy. Two Cases Presentation: First case, 1 months-old boy brought to the general hospital with chief complaint of fever. Patient had decreased of consciousness and bulging of anterior fontanella. Analysis of cerebrospinal fluid (CSF) showed Pandy test (+4) and None test (+4), high protein 369 mg/dl (mononuclear 44%, polymorphonuclear 56%), liquor glucose 2 mg/dl, CSF culture and blood culture resulted salmonella. Electrolyte and blood sugar was normal, complete blood count showed leukocytes 13.96x 103/µL and mild normochromic normocytic anemia. Head CT scan revealed communicating hydrocephalus. Second case, 6 months-old boy brought to general hospital with seizure as chief complaint. Cerebrospinal fluid (CSF) analysis showed Pandy test (+4) and None test (+4), high protein 569 mg/dL, liquor glucose 26 mg/dL, CSF culture and blood culture results found salmonella sp. Head CT scan revealed subdural hygroma at frontoparietal. Patient was treated by 3rd generation of cephalosporins (ceftriaxone) for 4 weeks. Patient discharge from hospital. Summary: Management of salmonella meningitis include administration of empiric antibiotic, supportive treatment and management of complication. High dose of antibiotic is given empirically without waiting for the results of culture. Learning Points: Clinical manifestations and outcome of meningitis salmonella

Challenges in Diagnosing Infective Endocarditis: A Case Report

Introduction: Infective endocarditis (IE) is an infection that affects the endocardial surface of the heart. Enforcing the diagnosis of IE is quite easy, but in some cases, it is sometimes very difficult to suspect the patient is experiencing an IE if the symptoms displayed are atypical or non-specific, so that the diagnosis and treatment are too late Case illustrations: A 51-year-old man was first referred from a Type C Hospital to the Emergency Room of Type B Hospital with diagnosis of congestive hepatopathy, transaminitis, hyperkalemia, hyponatremia related retention, suspected hypoalbuminemia due to chronic inflammation and hepatopathy, mild normochromic normocytic anemia due to chronic disease, pneumonia, sepsis, AKI (acute kidney injury) with differential diagnose ACKD (acute on chronic kidney disease) because suspect of prerenal suspicion that had been improving. Infective Endocarditis (IE) was diagnosed with modified Duke criteria, in which this patient found vegetation on the aortic valve 1.70 cmx0.66 cm. Treatment for patients was given empirical antibiotics (ampicillin 3 grams every 6 hours by intravenous/IV and gentamicin 180 mg every 24 hours by intravenous/IV) while waiting for blood culture results and the patient was referred to the Central General Hospital/Type A Hospital for further treatment. Conclusion: Infective Endocarditis is still a challenge in the field of medicine with its low incidence. In this case report, the patient experienced a clinical spectrum that was less specific for IE, causing difficulties in early diagnosis and management Keywords: Infective Endocarditis, Modified Duke Criteria, Aortic valve

Polymyalgia Rheumatica Evolved into RS3PE Syndrome. What is the Culprit: Idiopathic or Secondary, Following mRNA-Based COVID-19 Vaccines? A Case Report and Brief Review of the Literature

We describe the clinical case of a 74-year-old male patient who received the second Comirnaty/Pfizer anti-COVID-19 vaccine dose. After 3 weeks he showed the clinical signs of polymyalgia rheumatica. The history included mild chronic normocytic normochromic anemia and hypogammaglobulinemia, osteoarthritis disease, livedo reticularis, hypercholesterolemia, and arterial hypertension. Despite prolonged treatment with NSAIDs and dexamethasone, the disease evolved into remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Neoplastic diseases and associated collagen diseases were excluded. The clinical picture recurred, soon after, the booster dose of the Spikevax/Moderna vaccine. The inflammatory indices were high, the radiographs of the hands were free of erosions, the ultrasound investigations revealed bursitis of the shoulders, knee synovitis, marked subcutaneous edema of the lower limbs, hydrocele, bilateral Baker's cyst in the popliteal cavity, hematoma of a calf. The clinical picture, markedly improved, with oral prednisolone and was stabilized with the association of hydroxychloroquine. The finding of persistent hypomagnesemia was related to chronic intake of esomeprazole. The reports of rheumatological reactions in international databases and the rare cases of RS3PE <u>s</u>yndrome following the COVID-19 vaccine described in the literature are considered.

Prevalence and types of anemia among people with tuberculosis in Africa: a systematic review and meta-analysis

Globally, tuberculosis (TB) and anemia are public health problems related with high morbidity and mortality. Furthermore, anemia is frequently manifested among people with TB in Africa, prevalence ranging from 25 to 99%. The presence of anemia is associated with an increase in individuals’ susceptibility to TB and poor treatment outcomes. Studies have reported heterogeneous estimate of prevalence of anemia among people with TB in Africa. This review aimed to estimate the prevalence of anemia among newly diagnosed people with TB n Africa. We searched studies in Medline/PubMed, Cochrane library, ScienceDirect, JBI database, the Web of Science, Google Scholar, WorldCat, Open Grey, Scopus, Agency for Healthcare Research and Quality, ProQuest, and African Journals Online that reported the prevalence of anemia at TB diagnosis. Two reviewers performed data extraction with pre-defined inclusion criteria. A random-effects logistic regression model was used to pool the prevalence of anemia and levels of anemia with a 95% confidence interval (CI) in STATA version 14. Heterogeneity and publication biases were explored. A total of 1408 studies were initially identified, and seventeen studies with 4555 people with TB were included in the analysis. The prevalence of anemia among people with TB in Africa was 69% (95% CI 60.57–77.51). The pooled prevalence of anemia of chronic disease was 48% (95% CI 13.31–82.75) and normocytic normochromic anemia was 32% (95% CI 13.74–50.94) while mild anemia was 34% (95% CI 20.44–46.86). Females were more anemic than males at TB diagnosis in Africa (74% vs. 66%). The finding indicates that anemia is a common co-morbidity present among people with TB, especially among females. Mild anemia and normocytic normochromic anemia were more common at TB diagnosis. The finding indicates that anemia is a common co-morbidity present among people with TB in Africa region. Hence, it is recommended to instigate a routine anemia screening at TB diagnosis to improve treatment outcomes.

Multiple painful vesicles in a patient with erythroderma

A 50-year-old male with a history of alcoholism was evaluated for a 4-week history of painful vesicles and hemorrhagic erosions on the face without any previous treatment (Figs 1 and 2). He had a 15-year history of eczematous plaques on flexural surfaces with periods of remission and relapse. Over the last year, the patient developed widespread erythema with diffuse scaling and lower-limb edema. Laboratory tests revealed mild normochromic normocytic anemia (Hb 11.8 g/dL, MCV 94.3 fL, MCH 33.5 pg) with eosinophilia (13%), and abnormal liver function tests (ALT 15.1 U/L, AST 67 U/L, AST/ALT ratio 4.4).

37-Year-Old Man With Headache and Nasal Congestion

37-Year-Old Man With Headache and Nasal Congestion

Cutaneous epitheliotropic T-cell lymphoma in a donkey – a case report

BackgroundCutaneous epitheliotropic T-cell lymphoma is a malignant tumour of the skin already reported in humans, dogs, cats, horses, and other species, but not previously in donkeys. The standard diagnosis is based on clinical, morphological and immunophenotypic data. Differentiation of malignant versus benign proliferation of lymphocytes is crucial; in ambiguous cases T-cell receptor gamma (TRG) molecular clonality should be tested. In the present paper, we report a case of mycosis fungoides diagnosed in a donkey whose diagnosis was based on clinical, histological and immunohistochemical aspects and a positive TRG clonality test.Case presentationA twenty-five-year-old donkey gelding was referred with a mildly pruritic, generalised and severe exfoliative dermatosis. Otherwise, the animal was clinically healthy, though mildly underweight. Dermatological examination revealed severe generalised alopecic and exfoliative dermatitis, occasionally eroded, with high number of large, thin, greyish scales. All mucocutaneous junctions except the hoofs were affected. Ectoparasites and dermatophytes were ruled out. The complete blood count and blood smear evaluation revealed mild normocytic normochromic anemia. The biochemistry panel showed mild hyperproteinemia with albumin within the normal range. Protein electrophoresis showed moderate polyclonal hypergammaglobulinemia. Histological findings were characterised by interface dermatitis with massive exocytosis in the epidermis of a homogenous population of lymphoid cells showing atypia. Clusters of neoplastic cells were present within the epidermis forming Pautrier “microabscesses”. These findings are consistent with cutaneous epitheliotropic lymphoma. Immunohistochemical staining revealed uniform labelling of the neoplastic cells for CD3, and lack of expression of CD20 (a B cell lineage associated marker). Molecular clonality PCR (PARR) was performed using equine TRG primers; this revealed a clonal rearrangement in a heavy polyclonal background. Transmission electronic microscopy showed multiple lymphocytes with convoluted or cerebriform nuclei.ConclusionsThis case report provides the first evidence of clinical, histopathological, immunophenotypic features, electron microscopy findings and molecular analysis of a cutaneous epitheliotropic T-cell lymphoma (mycosis fungoides) in a donkey. Our observations suggest that cutaneous T-cell lymphoma should be included in the differential diagnoses of exfoliative dermatitis, even those progressing in a chronic pattern and/or with few or no pruritus.

A Trapped Colon

A Trapped Colon

Hemophagocytosis by acute myeloid leukemia blasts associated to poor clinical outcomes.

A 74-year-old man was referred to the university hospital for fatigue, weight loss, and thrombocytopenia. Initial examination revealed maculopapular lesions on his body. Subsequent blood tests showed mild normocytic anemia (12.1 g/dL), thrombocytopenia (43 × 109/L), and 3% blast cells among leukocytes (14.17 × 109/L). Coagulation assessment found disseminated intravascular coagulation (DIC). Biopsy of cutaneous maculopapular lesions found a perivascular infiltration by blast cells in the dermis, diagnosing leukemia cutis. Bone marrow film described infiltration by 76% blast cells. Blast cells were depicted as typical monoblast. Several blast cells showed hemophagocytic activity on erythrocytes (Figure 1A,B) but more rarely on nucleated cells (Figure 1C,D). Flow cytometry immunophenotyping revealed an immature cell population accounting for 50% of bone marrow nucleated cells and harboring the following profile: CD4+, HLADR+, CD13low, CD33+, CD117+ (half of them), CD14+ (half of them), and CD34−. Cytogenetic investigations found an isolated loss of the Y chromosome. Next-Generation Sequencing identified three pathogenic variants: FLT3:c.2503G > T (p.Asp835Tyr) with 13% variant allele frequency (VAF), TET2:c.1304del (p.His435Profs*12) with 44% VAF and a rare JAK2 point mutation in exon 19, JAK2:c.2437T > G (p.Tyr813Asp) with 50% VAF. A diagnosis of acute monocytic/monoblastic leukemia (corresponding to French–American–British M5 of acute myeloid leukemia (AML)) was established according to WHO 2016 classification. Multidisciplinary consultation meeting agreed on chemotherapy treatment using Cytarabin and Venetoclax. Unfortunately, the patient developed a blood transfusion dependency, an aggravation of the cutaneous lesions, and a massive DIC at the start of his treatment and died 19 days later. Haemophagocytic blasts are described in AML and frequently associated with anomalies of chromosome band 8p11 including t(8;16)(p11;p13) KAT6A::CREBBP, inv(8)(p11q13) KAT6A::NCOA2, t(8;22)(p11;q13) KAT6A::EP300, or t(3;8;17)(q27;p11;q12), or to t(16;21)(p11;q22) with FUS::ERG fusion gene. Our report provides new cytogenetic and molecular insights into this rare entity. Some authors have underlined the recurrence of association of haemophagocytosis by blasts with DIC with worse clinical outcomes, based on analysis of the few reported cases and series. Up to now, this cytological feature is not included in the disease prognostic criteria, but this question should be seriously considered, given the recurrence of disappointing outcomes in clinical cases showing haemophagocytosis on bone marrow smears. VC acquired the clinical data and was the referent doctor. ND performed the cytological bone marrow analysis. LTD realized the flow cytometry analysis. BL realized molecular analysis. LV performed the cytogenetic analysis. ZG wrote the manuscript. All authors reviewed and approved the manuscript. The authors thank Susan L. Reeves and Myriam Kossaï in Department of Pathology, Centre Jean Perrin, Clermont-Ferrand, for their technical assistance as well as to Gaston Ouedraogo for proofreading in English. The authors have declared no conflict of interest.


 Meningoencefalitis bacteriana secundaria a una vaginitis en un canino: Relato de un caso

The bacterial meningoencephalitis is a neurological disorder that affects dogs and cats, and develops on migration of bacteria from infectious focus, near or far from the central nervous system through the bloodstream, breaking the hemato-encephalic barrier and reaching the brain and meninges. in that context, this work has by objective report a case of meningoencephalitis concomitant with vaginitis in a canine, female, without race defined, 3 years old, attend at Dr. Vicente Borelli's Veterinary Hospital located in Aracaju-SE. The animal had motor incoordination, inclination of the head for the right side and walked in circles. Physical examination, blood count, renal profile, liver profile and protein fraction, cystocentesis guided by ultrasound, physical-chemical analysis, urine culture, CSF collection for cytology and bacterial culture and collection of vaginal secretion for bacterial culture and antibiogram were performed. Finally, exploratory laparotomy was performed to discard uterine stump on physical examination, bilateral horizontal nystagmus, cervical stiffness, lack of response to deep pain, absence of cranial tibial reflex, proprioceptive deficit in the right posterior limb, and blackened vulvar secretion were found. The hemogram showed mild normochromic normocytic anemia, thrombocytopenia and monocytopenia. Renal and hepatic profiles and protein fraction showed no changes. Urinalysis showed a cloudy appearance, alkaline pH, presence of red blood cells and leukocytes, in addition to crystals such as amorphous and triple phosphate. In urine culture, growth, isolation and identification of the microorganism Streptococcus spp. The results found in the cytological examination of the CSF were a small amount of eosinophilic, amorphous, finely granular protein material, density and little increased proteins. Ultrasonography and exploratory laparotomy did not show any noteworthy changes, but they did help to rule out differential diagnoses of vaginitis. As for the microbiological exams of CSF samples and vaginal secretion, both genera of gram-positive bacteria Staphylococcus grew. Thus, the present report allowed us to conclude that vaginitis can trigger meningoencephalitis due to bacterial translocation through the bloodstream.

Algorithm for diagnosis of early Schistosoma haematobium using prodromal signs and symptoms in pre-school age children in an endemic district in Zimbabwe.

Prompt diagnosis of acute schistosomiasis benefits the individual and provides opportunities for early public health intervention. In endemic areas schistosomiasis is usually contracted during the first 5 years of life, thus it is critical to look at how the infection manifests in this age group. The aim of this study was to describe the prodromal signs and symptoms of early schistosomiasis infection, correlate these with early disease progression and risk score to develop an easy to use clinical algorithm to identify early Schistosoma haematobium infection cases in resource limited settings. Two hundred and four, preschool age children who were lifelong residence of a schistosomiasis endemic district and at high risk of acquiring schistosomiasis were followed up from July 2019 to December 2019, during high transmission season. The children received interval and standard full clinical evaluations and laboratory investigations for schistosomiasis by clinicians blinded from their schistosomiasis infection status. Diagnosis of S. haematobium was by urine filtration collected over three consecutive days. Signs and symptoms of schistosomiasis at first examination visit were compared to follow-up visits. Signs and symptoms common on the last schistosomiasis negative visit (before a subsequent positive) were assigned as early schistosomiasis infection (ESI), after possible alternative causes were ruled out. Logistic regression identified clinical predictors. A model based score was assigned to each predictor to create a risk for every child. An algorithm was created based on the predictor risk scores and validated on a separate cohort of 537 preschool age children. Twenty-one percent (42) of the participants were negative for S. haematobium infection at baseline but turned positive at follow-up. The ESI participants at the preceding S. haematobium negative visit had the following prodromal signs and symptoms in comparison to non-ESI participants; pruritic rash adjusted odds ratio (AOR) = 21.52 (95% CI 6.38-72.66), fever AOR = 82 (95% CI 10.98-612), abdominal pain AOR = 2.6 (95% CI 1.25-5.43), pallor AOR = 4 (95% CI 1.44-11.12) and a history of facial/body swelling within the previous month AOR = 7.31 (95% CI 3.49-15.33). Furthermore 16% of the ESI group had mild normocytic anaemia, whilst 2% had moderate normocytic anaemia. A risk score model was created using a rounded integer from the relative risks ratios. The diagnostic algorithm created had a sensitivity of 81% and a specificity of 96.9%, Positive predictive value = 87.2% and NPV was 95.2%. The area under the curve for the algorithm was 0.93 (0.90-0.97) in comparison with the urine dipstick AUC = 0.58 (0.48-0.69). There was a similar appearance in the validation cohort as in the derivative cohort. This study demonstrates for the first time prodromal signs and symptoms associated with early S. haematobium infection in pre-school age children. These prodromal signs and symptoms pave way for early intervention and management, thus decreasing the harm of late diagnosis. Our algorithm has the potential to assist in risk-stratifying pre-school age children for early S. haematobium infection. Independent validation of the algorithm on another cohort is needed to assess the utility further.

High clinical heterogeneity in a Chinese pedigree of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S)

BackgroundBeing a newly defined disease, RVCL-S is underrecognized by clinicians globally. It is an autosomal dominantly inherited small vessel disease caused by the heterozygous C-terminal frameshift mutation in TREX1 gene. RVCL-S is featured by cerebral dysfunction, retinopathy, and vasculopathy in multiple internal organs. Misdiagnosis may cause devastating consequences in patients, such as iatrogenic PML caused by misuse of immunosuppressants. Thus, increasing awareness of this disease is in urgent need.ResultsWe uncovered a large Chinese origin RVCL-S pedigree bearing the TREX1 mutation. A comprehensive characterization combining clinical, genetic, and neuropathological analysis was performed. The Intrafamilial comparison showed highly heterogeneous clinical phenotypes. Mutation carriers in our pedigree presented with retinopathy (8/13), seizures (2/13), increased intracranial pressure (1/13), mild cognitive impairment (3/13), stroke-like episode (3/13), mesenteric ischemia (1/13), nephropathy (9/13), ascites (3/13), hypertension (9/13), hyperlipidemia (3/8), hypoalbuminemia (3/8), normocytic anemia (3/8), subclinical hypothyroidism (1/8), hyperfibrinogenemia (1/8), hyperparathyroidism (2/8), and abnormal inflammatory markers (4/8). The constellation of symptoms is highly varied, making RVCL-S a challenging diagnosis. Comparison with reported RVCL-S pedigrees further revealed that the mesenteric ischemia is a novel clinical finding and the MRS pattern of brain lesions is emulating neoplasm and tumefactive demyelination.ConclusionOur reports characterize a highly heterogeneous RVCL-S pedigree, highlight the probability of misdiagnosis in clinical practice, and broaden the clinical spectrum of RVCL-S.

Epidermal Renewal after Treatment of Primary Canine Hypothyroidism using Levothyroxine

Background: Primary canine hypothyroidism, an endocrine disorder that causes imbalances in the hypothalamus-pituitarythyroid axis, is a common cause of endocrine dermatoses, which frequently presents with opaque dry brittle hair. Tissue changes are also visible, such as myxedema, hyperkeratosis, epidermal atrophy, alopecia, and others. This paper describes the skin changes caused by primary hypothyroidism in a female dog before and after treatment with levothyroxine.Case: This case study involved a 7-year-old Dalmatian bitch with a history of weight gain and changes such as rough dry brittle hair. For about a year, the dog also had also presented symmetrical erythematous and alopecia skin lesions in the regions of the hind limbs, lower back and tail, progressive lethargy and fatigue after exercise. A hemogram showed mild normocytic and normochromic regenerative anemia, as well as mild leukopenia and neutropenia. Biochemical tests revealed increased levels of creatinine, total cholesterol, and triglycerides. Skin biopsy revealed the presence of comedones in the epidermis and acanthosis and trichilemmal keratinization. Hormonal tests revealed high TSH and low free T4 and total T4 levels. A cervical ultrasound scan showed changes in the thyroid glands, with hypoechoic parenchyma, in addition to increased size of the right lobe, suggesting thyroiditis. Based on these exams, the patient was diagnosed with primary hypothyroidism, and treatment with levothyroxine was instituted.Discussion: Around 90% of dogs with hypothyroidism show a decrease in total T4 and about 65-75% of them show an increase in TSH levels. In endocrinopathy, there is a decrease in the expression of T3 receptors in the keratinocytes and genes responsible for epidermal renewal. Also, molecules that affect epidermal differentiation bind to intracellular receptors belonging to the steroid/thyroid hormone superfamily. In this study, however, the application of the minimum levothyroxine dose restored the normal epidermal pattern for the species and the remaining parameters returned to normal. The hormone T3 acts in the differentiation of keratinocytes, a fact that, although not yet proven, is believed to be indirect and mediated by the epidermal growth factor or by the expression of the genes responsible for the renewal of the epidermis. Besides, some effects on the epidermis caused by deficiency of thyroid hormones may be due to secondary vitamin A deficiency, which is necessary for epithelial differentiation and binding epidermal growth factor (EGF) to the cell. Still, there is a theory that sex hormones also affect the differentiation of the epidermis, as studies show that deficiency causes effects similar to those caused by hypothyroidism. Some studies indicate the investigation of the relationship between secondary vitamin D deficiency and the increased cellularity of the epidermis of the spayed hypothyroid female rats. Additionally, the mechanism of the formation of hyperkeratosis in hypothyroidism is not yet elucidated. T3 is known to regulate keratingene expression and perhaps also epidermal maturation, epithelial cycle, and normal keratin synthesis. The single treatment with levothyroxine in the female dog was effective in promoting the restoration of gene expression to T3 in keratinocytes.Keywords: dermatopathies, endocrinopathies, hypothyroidism, levothyroxine, synthetic hormone.

S2965 Melanoma Presenting as Upper Gastrointestinal Bleed: Rare Primary vs Metastasis of Unknown Origin

INTRODUCTION: Melanoma is the most serious form of skin cancer and the fifth most common cancer in the United States. It generally appears where melanocytes are found in abundance including the eyes, skin and anal region. When found in the GI tract, the overwhelming cause is metastatic spread. This manifests as abdominal pain, fatigue, GI bleeds and their sequelae. Primary gastric melanoma is an exceedingly rare entity requiring thorough physical examination and imaging in order to rule out metastatic disease as the cause. We present a case of GI bleed secondary to gastric melanoma in which no other primary lesion was noted. CASE DESCRIPTION/METHODS: A 92-year-old man with a history of non-melanotic skin cancer presented to the emergency department with a 3-day history of melena. He was found to be hemodynamically stable with a mild normocytic anemia. He had never had an EGD and most recent colonoscopy was 15 years prior, notable for only diverticulosis. EGD performed during admission was significant for a large cratered mass in the gastric body identified as the source of bleeding. Biopsies were taken of the mass and returned strongly positive for S-100, Melan-A and Sox-10, consistent with malignant melanoma. Further evaluation with dermatology as well as oncology involved a thorough physical exam with skin check, PET CT as well as MRI brain, none of which revealed any other primary lesion consistent with melanoma. Due to the patient’s age, a decision was made to treat non-surgically. He opted for single-agent immunotherapy with pembrolizumab. PET CT after four cycles showed that the lone site of uptake in the stomach was no longer hypermetabolic. Patient has since finished eight cycles of pembrolizumab. DISCUSSION: This is a case of gastric melanoma in which no primary oculocutaneous source was identified. Given the exceedingly rare incidence of primary gastric melanoma, cases like these raise the question of a regressed primary cutaneous melanoma. This case illustrates that when GI melanoma is identified, a thorough skin exam and PET imaging are warranted to rule out a more common primary source. However, a negative evaluation does not completely eliminate the possibility of metastasis from a more common origin.Figure 1.: Gastric Melanoma Prior to Biopsy.

S1973 Achalasia With Diffuse Esophageal Dilation Causing Tracheal Compression and Severe Asthma

INTRODUCTION: Achalasia is a rare esophageal disorder that is caused by the lack of relaxation of the lower esophageal sphincter, causing loss of peristalsis and a dilated esophagus. Patients present with various upper gastrointestinal complaints. Here, we present the case of a 16-year-old female with history of uncontrolled asthma, including intubation at age 14 for status asthmaticus, who was found to have a massively dilated esophagus causing compression of the trachea. Peroral endoscopic myotomy (POEM) was performed and she experienced complete regression of her asthma symptoms. CASE DESCRIPTION/METHODS: 16-year-old female with history of uncontrolled asthma presents to pulmonology clinic. Pulmonary function testing (PFT) demonstrates severe obstruction (FEV1 33%, FEV1/FVC 45%) with little improvement following a 5-day course of oral steroids. She endorses mild, nonproductive cough. She appears well, speaking full sentences and ambulating without difficulty. She has diminished breath sounds bilaterally. Labs reveal only mild normocytic anemia. She is started on intravenous steroids and inhaler therapy. CT chest without contrast shows diffusely distended esophagus filled with liquid and food debris, exerting mass effect on the trachea and proximal mainstem bronchi, as well as diffuse groundglass opacities and scattered pulmonary nodules. Upon further assessment, the patient endorses occasional dysphagia with solid foods. She has infrequent vomiting episodes but denies odynophagia or weight loss. Eckardt score is 5. EGD reveals dilation in the entire esophagus; EndoFLIP reveals decreased distensibility and absent contractility consistent with type I achalasia. The following day, POEM procedure is performed. Post-procedure Eckardt score is 0. She is discharged home on lansoprazole 30 mg twice daily for 2 months. Over the next 6 months, she experiences complete remission of her asthma symptoms and inhaler therapy is discontinued. She also has complete resolution of dysphagia and gains 50 pounds. DISCUSSION: In our case, the patient had worsening PFT despite adequate treatment for asthma. Chest CT found a dilated esophagus, which may have been present 2 years prior when she was intubated for status asthmaticus. Her respiratory symptoms regressed completely after POEM for achalasia. This case demonstrates the importance of diagnostic review, especially in cases of primary treatment failure. Maintaining a broad differential can help clinicians think critically and correct potential reversible causes.Figure 1.: Chest CT shows diffusely dilated esophagus, likely secondary to achalasia.Figure 2.: Dilated esophagus causing compression of proximal mainstem bronchus.Figure 3.: Liquid and food debris in dilated esophagus near the LES.

HIDDEN IN PLAIN SIGHT: NEW DIAGNOSIS OF PULMONARY ARTERIOVENOUS MALFORMATION AFTER ISCHEMIC COLITIS

SESSION TITLE: Medical Student/Resident Pulmonary Vascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary arteriovenous malformation (PAVM) is an abnormal connection between a pulmonary artery and vein, which allows blood to bypass the filter function of the capillary beds and delivers deoxygenated blood to the left heart. This condition often remains undiagnosed until thromboembolic complications present. We report the case of new diagnosis of PAVMs in a patient presenting with ischemic colitis. CASE PRESENTATION: A 58-year-old female presented with acute onset diffuse abdominal pain and emesis. She was afebrile and normotensive with nonspecific abdominal tenderness on examination. Laboratory data was significant for mild leukocytosis and normocytic anemia. Computer Topography (CT) abdomen and pelvis showed diffuse inflammation around the cecum, consistent with ischemic colitis. She underwent partial colectomy with ileostomy placement. Postoperatively, she developed acute hypoxemia. CT angiogram showed left lower lobe pulmonary embolus and multiple PAVMs (largest in left lower lobe). She was treated with anticoagulation. However, she remained hypoxic and required oxygen at discharge. Further history revealed episodic epistaxis since childhood, three prior stillbirths, miscarriage, and multiple strokes in her sister. Hypercoagulable work-up was negative. She was readmitted multiple times for hypoxia and has undergone numerous PAVM embolization procedures. Post-embolization bubble echocardiogram showed intra- and extra-cardiac shunt both confirmed by transesophageal echocardiogram. DISCUSSION: Most PAVMs are hereditary with over 80% occurring in association with hereditary hemorrhagic telangiectasia, an autosomal dominant vascular disorder. Less commonly, PAVMs are idiopathic or secondary to trauma, infection or due to hepatopulmonary syndrome. Previously viewed as rare conditions, recent data suggest PAVMs affect 1 in 2,600. Patients with PAVMs present with hypoxemia and paradoxical embolization complications, including stroke, brain abscess, and other end-organ ischemia as seen in our patient who presented with ischemic colitis. A history of recurrent nosebleeds since childhood and family history of strokes were subtle clues to the diagnosis, but as in many other cases, the PAVMs were not identified until she presented with a paradoxical thromboembolic event. Patient has persistent hypoxemia despite embolization, and we hypothesize that obliteration of the large PAVMs led to elevated pulmonary pressures, which opened the intra-cardiac shunt in addition to new intra-pulmonary shunts. CONCLUSIONS: Pulmonary AVMs often remain undetected in patients until a thromboembolic complication occurs. Increased awareness of variable presentations of pulmonary AVMs is essential for prompt diagnosis and treatment to prevent devastating complications. Reference #1: Shovlin, C. Pulmonary arteriovenous malformations. Am J Respir Crit Care Med. 2014 Dec 1; 190 (11): 1217-1228. Reference #2: Lovering, A et al. Pulmonary pathways and mechanisms regulating transpulmonary shunting into the general circulation: An update. Injury. 2010 Nov; 41(0 2): S16-S23. Reference #3: Lee, W et al. Contrast echocardiography remains positive after treatment of pulmonary arteriovenous malformations. Chest Journal. 2003 Feb; 123 (2): 351-358. DISCLOSURES: No relevant relationships by RAMYA GORTHI, source=Web Response No relevant relationships by John Mwangi, source=Web Response No relevant relationships by Mackenzie Steck, source=Web Response