Paraneoplastic Process Research Articles

6980 A Case Report Of Severe Hypercalcemia In Acute Decompensated Liver Cirrhosis

Abstract Disclosure: M.M. Eid: None. R.M. Sargis: None. Introduction: Hypercalcemia in advanced liver disease in the absence of malignancy is a rare condition. Case: A 26 year old female with history of liver cirrhosis secondary to alcohol use disorder, presented with hematemesis and ascites. She was diagnosed with acute decompensated liver cell failure and transferred to our facility for liver transplantation. On Day 10 of her hospital course, she had an acute rise in serum calcium (Ca) to 10.8 mg/dl (N 8.7-10.5),albumin (Alb) 2.6 g/dl, corrected calcium (CCa) 11.9mg/dl. On day 13 Ca peaked to 13.5 mg/dl, CCa 14 mg/dl, ionized Ca 6.5mg/dl (N 4.2-5.4 mg/dl). Serum Ca was normal on day 9, Ca 8.7mg/dl, Alb 2.5 g/dl and CCa 9.9 mg/dl. She was not taking lithium, vitamin A or antacid. No personal or family history of bone disorder, fracture or kidney stone. On exam, blood pressure 85/45, heart rate 110 bpm, jaundiced with abdominal distension and respiratory distress. Labs: hemoglobin 8.1 g/dl, WBC 32.5K/Ul, platelet 136 K/Ul, serum creatinine 1.82 mg/dl, Na 133 mmol/l, K 3.5 mmol/l, Total/Direct bilirubin 29.9/18.1 mg/dl, alkaline phosphatase 166 U/L, AST/ALT 60/42U/l, Mag 2.3 mg/dl, Phos 5 mg/dl, INR 3, PTT 50 sec, parathyroid hormone (PTH) 12 pg/ml (N12-88), TSH 1.02 mciu/ml (N 0.34-4), 25 hydroxy vitamin D 17 ng/ml (N 20-80), parathyroid related peptide (PTHrP) 3.9 pmol/l (N<3.4), 1,25 di-hydroxy vitamin D 9.8 pg/ml (N 19.9-79.3), alpha fetoprotein 9.1 ng/ml (N <9). Normal anti smooth muscle and anti mitochondrial antibodies. Negative viral hepatitis serology. CT abdomen did not reveal hepatobiliary mass or tumor nor kidney stone. She was intubated and mechanically ventilated. Vasopressor support was initiated. One dose of calcitonin 4 units/kg and zoledronic acid 4 mg were given. Serum Ca decreased to 12 mg/dl, CCa 12.6 mg/dL then to 10.2 mg/dl, CCa 11mg/dl within hrs. Calcium normalized to 8.4mg/dl, CCa 9.2 mg/dl, ionized Ca 4.3 mg/dl within 24 hrs. Her condition deteriorated and withdrawal of care was decided. Conclusion: Our case demonstrates non PTH and non vitamin D mediated severe hypercalcemia in setting of acute decompensated cirrhosis and absence of malignancy. Previous literature has noted poor prognosis of hypercalcemia with acute decompensated cirrhosis. While hypercalcemia in cirrhosis may arise from paraneoplastic processes, in absence of malignancy it is speculated that acute hypercalcemia may arise from the inflammatory mediators inducing osteoclastic bone resorption as osteoclast activating factor, prostaglandin and immobilization. Some reports found an association between hypercalcemia and elevations in bilirubin and creatinine(1). Further research is needed to understand the pathophysiology and the management of hypercalcemia in acute decompensated cirrhosis.

Sclerosing mesenteritis as a surgical problem: a review of the literature and own clinical observation

The problem of studying the pathology of mesenteric fat of the small intestine in surgical practice has not yet received enough attention. A number of questions remain unresolved regarding the etiology and pathogenesis of mesenteric diseases, their possible connection with benign and malignant diseases, methods of their laboratory and instrumental diagnosis, possible options for conservative and surgical treatment, as well as systematization and structuring of the classification. One of the poorly studied representatives of diseases of the mesentery of the small intestine continues to be Sclerosing mesenteritis, characterized by various histological variants of damage to mesenteric fat and a varied nonspecific clinical picture. Taken together, this leads to certain difficulties in diagnosis, patients seeking access to doctors of various profiles, which ultimately negatively affects the results of treatment and can lead to social maladjustment and possible disability. Reports on the occurrence of this pathology in the medical literature are few and, as a rule, describe extremely rare clinical cases. However, in recent years, the frequency of detection of this pathology continues to grow steadily, which is associated with the progressive aging of the population, a high degree of surgical activity in relation to urgent diseases of the abdominal organs, and the improvement of instrumental diagnostic methods. Issues of etiology, pathogenesis, differential diagnosis of this disease and its possible connection with the paraneoplastic process currently continue to cause debate. Further accumulation of clinical experience, a better understanding of the pathogenesis of the disease, and improvement of imaging techniques will allow us to develop clearer diagnostic and clinical criteria, narrow the diagnostic search and, ultimately, improve and standardize treatment. The article provides a review of the literature on this rare surgical pathology, presents our own clinical observation, and discusses diagnostic issues and treatment options for this disease.

QUINQUAUD’S DISEASE IN THE SPECTRUM OF CONCOMITANT DERMATOLOGIC PATHOLOGY

Cicatrical alopecia is one of the acute issues of modern dermatology due to a permanent cosmetic defect in the form of bald areas with non-recoverable loss of hair follicles. Interrelation of cicatrical alopecia with other dermatoses and somatic diseases is also topical. The article presents a clinical case of development of Quinquaud’s disease of the scalp combined with parapsoriasis lichenoides and multiple seborrheic keratosis on the top of already administered targeted therapy in connection with previously removed skin melanoma. Among the features of this pathology, we noted: appearance of rashes after a past oncological disease, erythema diffusely spreading throughout the entire scalp, multiple follicular pustules and rapid formation of cicatricial atrophy, severe itching and soreness, resistance to the ongoing therapy, as well as multiple rashes on the skin of body and extremities in the form of lichenoid papules and plaques. For differential diagnostics, multifocal biopsic examination of the skin was carried out, which showed presence of histologic signs of three dermatoses, which make up a spectrum of the concomitant pathology in the patient. Taking into account the important role of staphylococcal infection in the pathogenesis of Quinquaud’s disease and parapsoriasis lichenoides, we can assume similar pathogenetic mechanisms for the development of these diseases in the patient, associated with disorders of cutaneous microbiome. It is possible that a history of the oncological pathology and targeted therapy could lead to a decrease in resistance and suppression of the immune system, which was also a factor contributing to the development of concomitant dermatoses. Appearance of multiple eruptive seborrheic keratomas on skin of the body and extremities may be an indicator of a paraneoplastic process and require oncological screening. Understanding the causes and common factors of formation of dermatoses comorbid with cicatricial alopecia is extremely important for a dermatologist, because it allows performing early diagnostics in a timely manner, assigning treatment and preventing development of the permanent cosmetic defect leading to a decrease in the quality of life.

QUINQUAUD’S DISEASE IN THE SPECTRUM OF CONCOMITANT DERMATOLOGIC PATHOLOGY

Cicatrical alopecia is one of the acute issues of modern dermatology due to a permanent cosmetic defect in the form of bald areas with non-recoverable loss of hair follicles. Interrelation of cicatrical alopecia with other dermatoses and somatic diseases is also topical. The article presents a clinical case of development of Quinquaud’s disease of the scalp combined with parapsoriasis lichenoides and multiple seborrheic keratosis on the top of already administered targeted therapy in connection with previously removed skin melanoma. Among the features of this pathology, we noted: appearance of rashes after a past oncological disease, erythema diffusely spreading throughout the entire scalp, multiple follicular pustules and rapid formation of cicatricial atrophy, severe itching and soreness, resistance to the ongoing therapy, as well as multiple rashes on the skin of body and extremities in the form of lichenoid papules and plaques. For differential diagnostics, multifocal biopsic examination of the skin was carried out, which showed presence of histologic signs of three dermatoses, which make up a spectrum of the concomitant pathology in the patient. Taking into account the important role of staphylococcal infection in the pathogenesis of Quinquaud’s disease and parapsoriasis lichenoides, we can assume similar pathogenetic mechanisms for the development of these diseases in the patient, associated with disorders of cutaneous microbiome. It is possible that a history of the oncological pathology and targeted therapy could lead to a decrease in resistance and suppression of the immune system, which was also a factor contributing to the development of concomitant dermatoses. Appearance of multiple eruptive seborrheic keratomas on skin of the body and extremities may be an indicator of a paraneoplastic process and require oncological screening. Understanding the causes and common factors of formation of dermatoses comorbid with cicatricial alopecia is extremely important for a dermatologist, because it allows performing early diagnostics in a timely manner, assigning treatment and preventing development of the permanent cosmetic defect leading to a decrease in the quality of life.

Hashimoto's encephalitis - A case report

A 50 year-old woman with a background of focal epilepsy presented to Emergency Department (ED) in convulsive status epilepticus.After 1 year seizure-free on levetiracetam,she initially presented with headache, tremor, fatigue and general malaise. She was discharged, then re-presented to ED several days later in status epilepticus. Two doses of diazepam administered pre-hospital failed to terminate the seizure. She was loaded with phenytoin,intubated and ventilated and commenced on a midazolam infusion. She spent 7 days in neuro-intensive care and was discharged home on levetiracetam 1.5 g twice daily and phyentoin 250 mg twice daily.One month later, she re-presented to ED with 4 days of worsening tremors and reduced mobility. Physical examination revealed multifocal myoclonus. She had experienced significant cognitive decline and neuropsychiatric symptoms including severe anxiety, delusions and paranoia.InvestigationsImagingInitial MRI head with gadolinium showed marked symmetric abnormality within the white matter of both hemispheres extending into subcorticol regions, most predominant at the vertex and involving U fibres. The neuro-radiologist commented that the differential for these changes was broad, including an encephalitis, PML, meningitis or a leukoencephalopathy.Repeat MRI head 1 month later showed complete resolution of the white matter changes leaving no sequelae.Blood testsHer past medical history included subclinical hypothyroidism. Thyroid function tests showed an elevated TSH of 21.33 and thyroid peroxidase(TPO) antibody level of 188.0 IU/mL, with FT4 levels within normal range.Extensive relevant blood screen, including the following was all negative• NMDA, glycine receptor and anti-cardiolipin antibody• Connective tissue screen, anti-MPO and anti-PR3• Serum electrophoresis• Paraneoplastic antibody screen including Cerebellum IIF, MA2, MA1, amphiphysin, CV2(CRMP5), Anti-Ri (ANNA 2) Ab, Anti Yo Ab and Anti Hu Ab• HIV and syphilis serology• JC virus• Plasma amino acid, urine organic acid and ammoniaLumbar punctureCSF WCC 1/mm3CSF protein- 816 mg/LCSF viral PCR (including JC virus) and oligoclonal bands negativeEEG- normal background activity with no clear focal or diagnostic epileptiform abnormalities.Treatment and follow-upThe clinical picture, elevated TPO antibodies and absence of other relevant investigation abnormality raised Hashimoto's encephalitis as a potential unifying diagnosis. She had a good response to inpatient treatment with steroids, her neuropsychiatric features resolved and she has remained seizure-free since discharge. She remains under neurology outpatient follow-up.Discussion:It can be challenging to make a diagnosis of Hashimoto encephalitis, and other potential causes such as infection, metabolic or paraneoplastic processes must be rigorously ruled out (1). In this case, high titres of TPO alongside the clinical presentation with recurrent seizures and cognitive decline were key in making the diagnosis (2,3). Due to an overlap of features, including myoclonus and rapid cognitive decline, it was important to consider Creutzfeldt-Jakob disease (CJD) in the differential. We ruled out CJD due to the rapid response to steroid therapy and lack of typical EEG and MRI findings (4). Overall, due to low prevalence and non-specific MRI and EEG features, this diagnosis can be difficult to make and requires thorough systemic clinical assessment.

Anti-ZSCAN1 Autoantibodies Are a Feasible Diagnostic Marker for ROHHAD Syndrome Not Associated with a Tumor.

Recent studies have reported the presence of autoantibodies against zinc finger and SCAN domain-containing protein 1 (ZSCAN1) in the sera of patients with rapid-onset obesity with hypoventilation, hypothalamic and autonomic dysregulation (ROHHAD) syndrome associated with neuroendocrine tumors, suggesting immunologic and paraneoplastic processes as the pathologic underpinnings. Moreover, several hypothalamic regions, including the subfornical organ (SFO), were reported to exhibit antibody reactivity in a patient with ROHHAD syndrome not associated with a tumor. Whether ROHHAD syndrome not associated with a tumor is associated with anti-ZSCAN1 autoantibodies remains unclear. We used a comprehensive protein array analysis to identify candidate molecules in the sera of patients with ROHHAD syndrome and identified ZSCAN1 as a target antigen. We also found that ZSCAN1 was co-expressed at the site of antibody reactivity to the IgG in the patient serum observed in mouse SFOs and an enzyme-linked immunosorbent assay showed that >85% of the patients with ROHHAD syndrome were positive for anti-ZSCAN1 autoantibodies. These results suggest anti-ZSCAN1 autoantibodies as a feasible diagnostic marker in ROHHAD syndrome regardless of the presence of a tumor.

Anti-N-methyl-D-aspartate receptor-associated encephalitis: A review of clinicopathologic hallmarks and multimodal imaging manifestations.

Anti-N-methyl-D-aspartate receptor-associated encephalitis (NMDARE) is a rare immune-mediated neuroinflammatory condition characterized by the rapid onset of neuropsychiatric symptoms and autonomic dysfunction. The mechanism of pathogenesis remains incompletely understood, but is thought to be related to antibodies targeting the GluN1 subunit of the NMDA receptor with resultant downstream dysregulation of dopaminergic pathways. Young adults are most frequently affected; the median age at diagnosis is 21 years. There is a strong female predilection with a female sex predominance of 4:1. NMDARE often develops as a paraneoplastic process and is most commonly associated with ovarian teratoma. However, NMDARE has also been described in patients with small cell lung cancer, clear cell renal carcinoma, and other benign and malignant neoplasms. Diagnosis is based on correlation of the clinical presentation, electroencephalography, laboratory studies, and imaging. Computed tomography, positron emission tomography, and magnetic resonance imaging are essential to identify an underlying tumor, exclude clinicopathologic mimics, and predict the likelihood of long-term functional impairment. Nuclear imaging may be of value for prognostication and to assess the response to therapy. Treatment may involve high-dose corticosteroids, intravenous immunoglobulin, and plasma exchange. Herein, we review the hallmark clinicopathologic features and imaging findings of this rare but potentially devastating condition and summarize diagnostic criteria, treatment regimens, and proposed pathogenetic mechanisms.

Opsoclonus-myoclonus syndrome associated with West Nile virus

Opsoclonus is oculomotor dyskinesia characterized by rapid, repetitive conjugate eye movements that are involuntary, arrhythmic, chaotic, and multidirectional (horizontal, vertical, and torsional components). Most common cause of the symptom is paraneoplastic process. It is combined with myoclonus usually with the development of opsoclonus-myoclonus syndrome. Viral etiology is one of the possible causes of the of this syndrome, which is presented in the following case. A 26-year-old man was admitted to an infectious hospital suspected by encephalitis. After a 2-day febrile fever the patient developed balance problem, nausea, vomiting, tremors in the limbs and head, sensations of jerking of eyeballs. The neurological examination revealed opsoclonus, myoclonic jerking in the limbs, neck and trunk muscles, severe static and dynamic ataxia, there was no consciousness changes or altered mental stature. Cerebrospinal fluid examination revealed a pleocytosis (24 cells), increased protein levels (1.1 g/l). MRI of the brain was normal. After excluding of typical neuroinfections the patient was tested for West Nile fever. Elevated titers of IgG and IgM for West Nile fever virus were detected, as well as positive PCR for virus RNA in the cerebrospinal fluid. Patient was treated by acyclovir, an antibiotic and dexamethasone but severe neurological symptoms were persisted for 2 weeks with inability of sitting and walking. Then the symptoms gradually began to improve, rehabilitation was included with total recovery during the next 2 months. The doctors should be aware for possibility of neuroinvasive form of West Nile fever as the etiology of opsoclonus-myoclonus syndrome.

Antisynthetase syndrome: a case report and review of the literature.

antisynthetase syndrome is a rare autoimmune disease characterized byinterstitial lung disease, non-erosive arthritis, myositis, Raynaud's disease, and/or "mechanichand" when autoantibodies directed against aminoacyl-tRNA synthetases are detected.Antisynthetase syndrome belongs to the group of idiopathic inflammatory myopathies and isthe so-called overlap myositis. The article provides the latest literature data on the diagnosticvalue of myositis-specific autoantibodies based on a literature review for the period from2013 to 2023 using the scientometric databases MEDLINE/ PubMed, Wiley Online Library,and Scopus. Data from the literature show that certain myositis-specific autoantibodies,namely anti-PL-7 and anti-PL-12, can affect the risk of developing interstitial lung disease,and determine the course and prognosis of the disease. The presence of interstitial lungdisease in patients with myositis correlates with increased morbidity and mortality. Thearticle describes a clinical case of the debut of the antisynthetase syndrome from interstitiallung disease, which was falsely diagnosed as a coronavirus disease. The patient's condition
 improved only because of using glucocorticoids, which the patient stopped taking over time,which led to the worsening of pulmonary symptoms, the appearance of new clinical signs ofdamage to the joints and skin, progressive decrease in muscle function, and dysphagia. Afteran examination in the rheumatology department, based on the presence of interstitial lungdisease in the patient - fibrotic alveolitis, which was confirmed by computer tomography,myositis, arthritis, characteristic skin changes, the presence of antinuclear antibodies, anti-SS-A/Ro52, specific antisynthetase antibodies (Jo-1, Pl-7, Pl-12), the diagnosis of theantisynthetase syndrome was established. A detailed laboratory and instrumental examinationmade it possible to rule out a paraneoplastic process at the time of examination. Theprescribed treatment included pulse therapy with methylprednisolone and cyclophosphamide,which led to improvement in the patient's condition. The work carried out emphasizes theneed for interdisciplinary interaction of pulmonologists, rheumatologists, and infectiousdisease specialists at the stage of verification of the final diagnosis and the therapyappointment. Achieving clinical and laboratory remission of the disease requires long-termmonitoring by a rheumatologist.

Long term outcomes in patients with anti-DPPX autoimmunity

DDPX antibody-associated encephalitis is characterized by cognitive dysfunction, neuropsychiatric symptoms, and CNS hyperexcitability, preceded by prodromal weight loss and diarrhea. Data regarding long-term outcomes is scarce. We retrospectively identified six anti-DPPX encephalitis patients across all three Mayo Clinic sites with inclusion criteria: 1) positive DPPX cell-based assay and mouse tissue-based immunofluorescence samples in both serum and CSF; 2) duration of follow up of at least 36 months from symptom onset to last follow up. Only one patient had a paraneoplastic process in the setting of chronic lymphocytic leukemia. At last follow up, all patients had resolution of GI symptoms. Residual cognitive impairment was seen in 4/6 (67%). Clinical stability was reached in 3/6 (50%) while on immunotherapy. Immunotherapy was discontinued in 2/6 (33%) and they remained stable without relapse at last follow up. One patient died of unclear etiology. Overall long-term outcomes are good in anti-DPPX encephalitis. Symptoms can improve on immunotherapy, but full resolution and return to premorbid baseline is unlikely.

DP12 Painful oral keratosis and skin lesions: a paraneoplastic diagnostic conundrum

Abstract A 70-year-old man was referred to oral medicine with extensive, painful oral hyperkeratosis affecting the tongue, buccal mucosa and palate. Medical history included a previous diagnosis of prostate cancer. Histology from multiple oral biopsy specimens showed only hyperparakeratosis and acanthosis, with no fungi or dysplasia. Owing to the absence of oral inflammation, the pain was treated as neuropathic. The patient then developed skin lesions and dermatology review was requested. Skin examination revealed marked hyperkeratotic, verrucous plaques affecting the extensor surfaces of the limbs and dorsal hands, as well as the plantar feet bilaterally. The nails were unaffected. There was violaceous discolouration of the pinnae. Given the history of prostate cancer, a paraneoplastic process was suspected. Two incisional biopsies were taken, which showed epidermal acanthosis with necrotic and dyskeratotic keratinocytes throughout the epidermis. There was a dense eosinophilic inflammatory infiltrate. Direct and indirect immunofluorescence was negative. The appearances were suggestive of a paraneoplastic phenomenon, including acrokeratosis paraneoplastica. Haematological investigations identified an IgG monoclonal paraproteinaemia with raised kappa:lambda ratio. Following further investigation, including bone marrow biopsy and positron emission tomography computed tomography, a diagnosis of monoclonal gammopathy of undetermined significance was made by haematology. A repeat bone marrow biopsy 7 months later confirmed evolution to myeloma. As CRAB criteria (hypercalcaemia, renal insufficiency, anaemia and bone lesions) were absent, a period of observation followed. A trial of oral steroids improved the cutaneous eruption, but he developed significant side-effects. Oral mycophenolate, methotrexate and acitretin were used as steroid-sparing agents, with a poor clinical response. The skin lesions progressed to a widespread psoriasiform eruption on the trunk and lower limbs with the formation of bullae. Further biopsies showed an eosinophil-rich infiltrate with negative immunofluorescence, raising the possibility of an eosinophilic dermatosis of haematological malignancy. After 2 years, given the worsening skin symptoms, it was decided to commence bortezomib, cyclophosphamide and dexamethasone (VCD) chemotherapy. Despite four cycles of VCD treatment, the skin lesions worsened and as the paraprotein levels did not reduce, treatment was stopped. Subsequently, further elevations in serum free light chains prompted treatment with lenalidomide. This resulted in a marked improvement in the skin and reduced pain from the oral lesions, as well as a reduction in serum free light chains. Acrokeratosis paraneoplastica (Bazex syndrome) is characterized by digital hyperkeratosis and paronychia, which may progress to involve the limbs and trunk. Eosinophilic dermatosis of haematological malignancy is characterized by a pruritic, papular skin eruption with a vesiculobullous component. This case presents a diagnostic conundrum, with evolving features of two different paraneoplastic conditions.

ID: 216851 Use of Peripheral Nerve Stimulation for Lower Extremity Pain Due to Paraneoplastic Disorder

A 73-year-old male with history of prostate cancer s/p resection admitted for multiple progressive mononeuropathies with a significant component of pain, specifically to his right lower extremity, was evaluated for consideration of peripheral nerve stimulation (PNS). The pain radiated from his right knee to his foot along the medial aspect, existed for four months, and was described as throbbing and burning that never resolved for which he required systemic opioids and multimodal analgesics. Given the progression of multiple mononeuropathies including cranial nerves, multiple lung nodules on imaging, and non-diagnostic nerve and muscle biopsies, the most likely etiology was paraneoplastic process, most likely lung or recurrence of prostate cancer. The patient underwent treatment with steroids, IVIG, and PLEX for the paraneoplastic disorder. The patient was considered for PNS to help alleviate his right lower extremity pain.

An Atypical Presentation of GABA-B Encephalitis (P5-5.023)

<h3>Objective:</h3> N/A <h3>Background:</h3> GABA-B receptor encephalitis is a cell surface mediated paraneoplastic disease secondary to antibody production resulting in neuronal cells loss, microglial proliferation, and preferentially targets the limbic system. Symptoms include seizures, memory loss, confusion, and altered behavior. The infrequency with which it is encountered can create a diagnostic challenge. <h3>Case Description:</h3> A 73-year-old female presented as a referral months post hospitalization and outpatient evaluation. Initial presentation began with subacute progressive disorientation, crying spells, ageusia, anosmia, and memory loss without a known precedent illness. On initial exam she was alert, oriented only to self, inattentive, and without other focality. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> The results of the work up included contrasted MRI demonstrating T2 hyperintensities within the hippocampi. Lumbar puncture revealed antibodies against GABA-B receptors. High dose steroids were initiated with minimal improvement therefore IVIG was trialed in the outpatient setting resulting in stabilization and moderate improvement of symptoms. A PET scan was requested and revealed a mass within the left lower lobe of the lung. Biopsy identified features of small cell carcinoma confirming our suspicion of encephalitis secondary to paraneoplastic syndrome. Currently she is undergoing oncological evaluation and treatment. Symptoms remain stable, but emotional lability, poor short-term recall, ageusia and anosmia persist. No additional IVIG or long-term immunotherapy was initiated as treatment should be targeted toward the malignancy. She will remain under neurological surveillance with serial exams and MRIs. <h3>Conclusions:</h3> This case illustrates the importance of recognizing alternative causes of encephalitis. Localizing limbic symptoms were present although the lack of seizures and presence of ageusia and anosmia is highly unusual. We also discovered an extensive smoking history and family history of lung cancer. These red flags highlight the need for a complete history. Early consideration of a paraneoplastic process causing encephalitis will facilitate additional diagnostic testing, prompt initiation of immunotherapy and accurate diagnosis. <b>Disclosure:</b> Dr. DeHart-McCoyle has nothing to disclose. Dr. Chen has nothing to disclose.

E019 A case of RS3PE triggered by immune check point inhibitor

Abstract Background/Aims Immune checkpoint inhibitors (ICIs) are increasingly being used in oncology and there is growing evidence of rheumatological problems arising in these group of patients. ICIs have been approved for the treatment of several cancers including non-small cell lung cancer, renal cell carcinoma, Hodgkin lymphoma and other malignancies. Pembrolizumab, an anti-PD1, is known to cause inflammatory arthritis in some patients, and we report a case of relapsing-remitting synovitis with pedal oedema (RS3PE) in a patient with lung cancer. Methods A 67-year-old lady was diagnosed with adenocarcinoma in her left lung with pleural and pulmonary metastasis. She was commenced on carboplatin, pemetrexed and pembrolizumab initially for 4 cycles followed by pembrolizumab maintenance therapy for another 2 years. However, while on pembrolizumab therapy, she started to develop intermittent pain and swelling in her small joints of the hands and feet. There was marked pitting pedal oedema extending up to the knee along with swelling of the dorsum of the hand. She had intermittent swelling in the knee joints as well. Results The blood tests were negative for rheumatoid factor, anti-CCP and ANA. The CRP was markedly raised (120) from her previous values since she started developing joint symptoms. The kidney and liver function tests were within normal limits. A CT chest, abdomen pelvis was done which did not reveal any metastasis or progression of lung cancer. At the time of the review she was started on prednisolone 20mg once daily. Following this, the joint pain and swelling started to resolve, and the patient was advised to taper the steroids gradually. The pembrolizumab therapy was stopped few months later. The pedal oedema resolved within a few weeks of starting steroids and the joint inflammation settled after stopping the treatment. Conclusion ICI therapy has been known to trigger inflammatory arthropathy like RA. Psoriatic arthritis, undifferentiated monoarthritis and oligoarthritis, RS3PE and tenosynovitis have also been reported. Most published cases are mild to moderate in severity often responding to corticosteroids. Several patients have been treated with traditional DMARDs and biologics. RS3PE syndrome could be part of the paraneoplastic process but the onset of symptoms after starting pembrolizumab and rapid resolution after stopping the treatment indicates that this is likely a drug-induced adverse effect. Disclosure D. Ramachandran: None. W. Mushtaq: None. D. Makkuni: None.

Leser–Trelat sign in cosmetologist’s practice

LeserTrelat syndrome (eruptive seborrheic keratosis) is an unusial paraneoplastic dermatosis characterized by sudden appearance of seborrheic keratomas on the skin and a progressive increase of their number. This condition was first described in 1901 by the German surgeon E. Leser and the French surgeon U. Trelat. It occurs with the same frequency in both men and women aged 40+. The etiology and pathogenesis have not been studied in detail, however, there is evidence that the development of the syndrome may be associated with stimulation of the epidermal growth factor, which leads to stimulation of keratinocytes. The manifestation of the syndrome is usually start at the same time with cancer development, mostly it can be combained with adenocarcinoma of the gastrointestinal tract (47.7%), with intestinal carcinoma (32%), with lymphoproliferative diseases (21%), less often with malignant neoplasms of the lungs, breast, prostate.&#x0D; The clinical picture of the LeserTrelat sign is characterized by the sudden appearance оf seborrheic keratomas, which have typical clinical and histological signs. The most typical localization of seborrheic keratosis are back and chest (76%), limbs (18%), face (21%), abdomen (15%), neck (13%), armpits (6%), inguinal folds (3%). Keratosis can appear rapidly, over several months or even weeks. The rapid appearance of multiple seborheic keratomas may precede or develop with the oncological process in the internal organs.&#x0D; Treatment is carried out at the same time with the establishment and treatment of the underlying disease and consists in removing the largest keratomas by destructive methods (surgical excision, radiowave method, cryodestruction, electrocoagulation).&#x0D; The prognosis is favorable if paraneoplastic process was early detected.&#x0D; The article describes clinical cases of multiple seborrheic keratosis and the tactics of examining this group of patients.

Case of granulomatosis with polyangiitis: optimal possibilities for rapid diagnosis in a multidisciplinary hospital

Introduction. One of the distinguishing features of systemic vasculitis is their manifestation under the guise of a lesion of one or another organ system, which is often multi-organ in nature with signs of systemic inflammation. The latter is interpreted primarily as part of an infectious or paraneoplastic process, which causes a delay in the diagnosis.The aim of the study was to present the diversity of the clinical picture in vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA), the speed and large volume of diagnostic measures with the effective cooperation of therapeutic and surgical specialists, radiologists on the way to verifying granulomatosis with polyangiitis in a young woman.Materials and methods. Patient K., 46 y. o., was hospitalized in the Otolaryngology Department of the N.I. Pirogov City Clinical Hospital No. 1 of the Moscow Health Department with complaints of hearing loss, pain and stuffiness in the left ear, unproductive cough, hoarseness and fever up to 38.5 °C. According to the radiography (RG) of the chest organs, right-sided pneumonia was detected. Conducted antibiotic therapy without effect. As part of the differential diagnostic search, the following nosologies were excluded: infective endocarditis, sepsis, tuberculosis, primary multiple or central lung cancer complicated by paracancer pneumonia, metastatic lesion, infectious, brucellosis spondylodiscitis.Results. In the blood test, attention was drawn to a decrease in the level of hemoglobin to 111 g / l, an increase in the rate of erythrocyte sedimentation to 45 mm / h and the level of C-reactive protein to 142 mg / l, microhematuria according to the general urine analysis. Instrumental research methods – RG of 16.02.22, MSCT of the chest organs on 17.02.22, 27.02.22, 10.03.22 showed progressive bilateral focal pneumonia with a focus of consolidation in the middle lobe, EchoCG, ultrasound of the abdominal cavity and small pelvis, RG of the temporal bone, bronchoscopy with bronchoalveolar lavage and microscopic analysis, for atypia and bacteriological culture. A gynecological examination and a smear from the cervical canal for microscopic analysis were performed, atypical cells, consulted by a phthisiatrician (no data for tuberculosis), consulted three times by a thoracic surgeon (exclusion of volumetric formation of the middle lobe of the right lung). Given the history and clinical presentation (female gender, young age, bilateral otitis media, hoarseness, and destructive nature of pneumonia), granulomatosis with polyangiitis was suspected, and tests for ANCA were prescribed. A transthoracic biopsy of the right lung was performed. A rheumatologist prescribed induction pulse therapy with corticosteroids, and after serological and histological confirmation (antibodies to Proteinase-3 Anti-PR3 &gt; 200 IU / ml, productive pneumonitis, granulomas without signs of tuberculosis), immunosuppressive therapy with cyclophosphamide. Against the background of pathogenetic treatment, a pronounced clinical and laboratory effect was noted.Conclusion. In this clinical situation, the simultaneous involvement of specialists of various profiles, the performance of a large number of laboratory and instrumental studies in dynamics, the absence of delay in histological verification made it possible to quickly exclude common diseases in the population and suspect systemic vasculitis, establishing a correct diagnosis within 5 weeks of the hospitalization period.

Risk factors for the occurrence and development of paraneoplastic ophthalmopathies in dogs and cats

The frequency of oncological diseases in animals is becoming more and more every year. The development of diagnostic studies, the development of new treatment protocols contributes in some cases to improving the prognosis of the disease. However, a big problem is the development of paraneoplastic syndromes in various oncological pathologies, which leads, on the contrary, to a deterioration in the prognosis. There is no specific treatment for paraneoplastic processes – improvement of the condition and disappearance of paraneoplastic manifestations is the result of treatment of the primary tumor. Cancer-associated ophthalmopathies, such as paraneoplastic syndrome, are no exception. In addition to secondary eye pathologies, intraocular neoplasms are also found against the background of oncological processes. Intraocular tumors in animals are relatively rare neoplasms, there are both malignant and benign tumor processes. In dogs, we most often encounter pigmented melanomas, less often with squamous cell carcinoma and sarcomas of an unclear phenotype. In cats, the most common intraocular pathology is melanoma, followed by lymphoma and posttraumatic sarcoma of the orbit of the eye is not uncommon. They can develop in both elderly animals and animals of a younger age group. This article presents the results of studies of risk factors for the occurrence and development of immune-mediated paraneoplastic ophthalmopathies in dogs and cats. The article discusses the possible causes of the development of ophthalmic paraneoplastic pathologies, the etiopathogenesis of which includes a number of factors. The possibilities of innovative diagnostic methods, such as magnetic resonance imaging and computed tomography, complete ophthalmological examination using modern ophthalmological equipment, are considered. And the variants of morphological diagnoses are presented, in which cancer-associated ophthalmopathies most often develop.

Тhe clinical case of benign monomelic amyotrophy of the lower limb

The benign monomelic amyotrophy of the lower limb is a slowly progressive disease that is clinically manifested by muscle atrophy in only one lower limb. This disease is quite rare, while it is most common in Asian countries (about 80 cases have been described). According to the literature a total of 16 cases of benign monomelic amyotrophy of the lower limb were described in Europe by 2000. Etiology and pathogenesis have not been reliably studied now. The article presents a clinical case of the development of this disease in a 42-year-old patient. The patient was admitted with complaints of weakness in the right leg and its decrease in volume. During the period of hospitalization, diff erential diagnosis was carried out with amyotrophic lateral sclerosis, progressive muscle atrophy, Hirayama disease, vascular and paraneoplastic processes. According to the results of a comprehensive laboratory and instrumental examination, the diagnosis was fi rst established: benign monomelic amyotrophy of the lower limb. The father of a patient who had atrophy of the muscles of the left lower limb would also be examined. According to the data of hereditary anamnesis, an assumption was made about the presence of the phenomenon of anticipation in the inheritance of benign monomelic amyotrophy of the lower limb. This article describes for the fi rst time a case of benign monomelic amyotrophy of the lower limb in the domestic literature, as well as a familial case of this disease all over the world.

Вирусные инфекции – причина или триггер развития гемобластоза?

In recent decades, there has been an increase in the number of oncological cases in children. Most common diseases are hemoblastoses, which are characterized by clinical polymorphism in the disease onset, so differential diagnosis should be made. This article presents a clinical case of serous meningitis in a child with increasing dynamics of lymphocytic pleocytosis. The clinical diagnosis of lymphocytic choriomeningitis was based on clinical and anamnestic data (accommodation in the private sector, moderate severity of the general infectious syndrome in combination with severe cerebral and meningeal symptoms), laboratory data (increasing lymphocytic pleocytosis and cell-protein dissociation in the cerebrospinal fluid). The therapy correction included antiviral therapy, which helped to achieve normalization of the cerebrospinal fluid and clinical recovery of the child from an acute neuroinfectious disease in a short time. This clinical case is unique in that 2.5 months after the disease onset, the patient developed convergent strabismus and was hospitalized. Routine blood analysis revealed 25% of blast forms. Further, the diagnosis of acute lymphoblastic leukemia was confirmed, and specific therapy was initiated. It is generally recognized that a prolonged infectious process can be a trigger for both autoimmune and paraneoplastic processes, so long-time patient observation should be provided by a group of specialists (pediatrician, neurologist, infectionist, etc.), and control laboratory examination should be done. Key words: herpesviruses, children, leukemia, lymphocytic choriomeningitis, meningitis, cytoflavin

Giant perianal seborrheic keratosis as a manifestation of the Leser-Trelat syndrome

Seborrheic keratosis is the most common benign tumor of the epidermis. Rarely the tumor develops in the perineal area and quite rarely is large. For the Leser-Trelat syndrome these tumors is a marker of a malignant disease even before the symptoms are appeared, as well as a manifestation of the paraneoplastic process. In our case report, a giant perianal seborrheic keratoma was the reason for the clinical examination of the patient and stomach cancer was detected. As a result, we demonstrated a successful experience of surgical treatment of seborrheic keratoma of the perianal area and determined an algorithm for the treatment of stomach cancer.