A review of proton pump inhibitor photosensitivity in a tertiary referral photodiagnostic centre

Over the last few years, we have seen 11 patients presenting with proton pump inhibitor (PPI) photosensitivity at our tertiary referral photodiagnostic service and in our local dermatology department. Many adverse effects, including the discovery in 2020 of an almost twofold increased risk of severe COVID-19, of this widely used group of drugs have been noted (Lee SW, Ha EK, Yeniova AO et al. Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching. Gut 2020;DOI: 10.1136/gutjnl-2020-322248). Although PPIinduced phototoxicity has been described, phototest results have not been reported and all clinical presentations have not been described. We aimed to identify all patients with PPI photosensitivity who presented to our unit. We sought to better understand their clinical characteristics, blood test results and photodiagnostic results. We retrospectively reviewed all case notes and investigation results of patients who were diagnosed with PPI photosensitivity. Eleven patients were identified to have been seen between 2014 and 2019. Two patients were male and nine were female. Mean duration of disease was 3 6 years and mean duration of PPI ingestion was 5 years. Five patients presented with a drug-induced lupus pattern [subcutaneous lupus erythematosus (SCLE;n = 2), papulosquamous SCLE and discoid (n = 1), tumid (n = 1) and acute cutaneous (n = 1)], four with drug-induced phototoxicity (sunburn-like) and two with a drug-induced solar urticaria relating to a lupus mechanism. The majority of patients reported symptoms on sun-exposed sites. The most common indication for PPI prescription was gastroesophageal reflux disease with omeprazole being the most commonly prescribed PPI. All patients underwent phototesting. Three patients were not on an PPI while undergoing phototesting and did not demonstrate photosensitivity. Of the remaining patients who underwent phototesting the most common finding was delayed sensitivity to ultraviolet A and to visible light. Druginduced photosensitivity can be a challenging diagnostic entity owing to the varied clinical presentation and heterogeneous time to onset. We present this case series to further help clinicians in recognizing the clinical and diagnostic pattern of photosensitivity present with PPI use.

TUBERCULOUS PLEURAL EFFUSION MASQUERADING AS DRUG-INDUCED LUPUS

SESSION TITLE: Critical Care Presentations of TB SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: TNFα plays a pivotal role in inflammation and maintenance of immune response against tuberculosis. The use of TNF inhibitors (TNFi) is associated with a significant increase in the incidence of tuberculosis (TB). TNFi may cause drug-induced lupus (ATIL) presenting as constitutional symptoms, rashes, pericardial and pleural effusions with positive autoantibodies. We present a case of pleural TB masquerading as drug-induced lupus. CASE PRESENTATION: A 68y/o woman with a history of ulcerative colitis (on infliximab, mesalamine), hypertension, T2DM, CAD, complained of low-grade fever, rashes, left-sided chest pain, dyspnea, and arthralgias for two weeks. Chest pain- worse with inspiration and cough. She emigrated from India to the USA 40 years ago. Six months before infliximab therapy, Quantiferon gold was negative. Exam: faint hyperpigmentation over shins, minimal swelling of MCPs and ankles, dullness to percussion over the left chest with decreased breath sounds. Labs: CRP 101 mg/dL, Hb 10.8 iron deficient, rheumatoid factor and anti-CCP negative, ANA 1:40, dsDNA 1:640, a reminder of ENA negative, anti-histone negative, C3/C4 normal, UA bland, protein/Cr 0.4 mg/gm, negative blood cultures, SPEP and LDH normal. CXR: opacification of the left lung up to midfield. CT chest: moderate left and small right pleural effusions, enlarged mediastinal lymph nodes. COVID and Quantiferon: negative. Thoracentesis: 850 ml of exudative fluid (2 out of 3 Light's criteria), lymphocytic predominance (76% of 4148 nucleated cells), adenosine deaminase (ADA) 42 U/L, gram stain, culture, acid-fast and MTB PCR negative, cytology negative. Thoracoscopy with biopsy of the parietal pleura: necrotizing granulomatous pleuritis with acid-fast bacilli. Sensitivity: pan-sensitive M. tuberculosis. Sputum: negative for TB. She was discharged on RIPE treatment for reactivation of TB. DISCUSSION: The incidence of infliximab-induced lupus is approximately 0.19% and confirming the diagnosis is challenging. The immunogenicity of infliximab is high, 66% of patients develop positive ANA. Anti-histone antibodies are less commonly associated with ATIL as opposed to classic drug-induced lupus and dsDNA is positive in up to 90% of cases of ATIL. Renal involvement is rare. The diagnostic usefulness of ADA (over 40 U/L) in lymphocytic pleural effusions for the diagnosis of tuberculosis in an immunosuppressed individual is demonstrated here. In countries with low TB burden, such as the USA, the positive predictive value of ADA in pleural fluid declines but the negative predictive value remains high. CONCLUSIONS: Tuberculous pleuritis is not always easily diagnosed since AFB smears and sputum may remain negative. When ADA level in lymphocytic pleural fluid is not low thorough search for TB with thoracoscopy and biopsy is justified. Reference #1: Shovman O, Tamar S, Amital H, Watad A, Shoenfeld Y. Diverse patterns of anti-TNF-α-induced lupus: case series and review of the literature. Clin Rheumatol. 2018 Feb;37(2):563-568. Reference #2: Benucci, M., Gobbi, F. L., Fossi, F., Manfredi, M. & Del Rosso, A. (2005). Drug-Induced Lupus After Treatment With Infliximab in Rheumatoid Arthritis. JCR: Journal of Clinical Rheumatology, 11 (1), 47-49. Reference #3: Valdés L, San José ME, Pose A, Gude F, González-Barcala FJ, Alvarez-Dobaño JM, Sahn SA. Diagnosing tuberculous pleural effusion using clinical data and pleural fluid analysis A study of patients less than 40 years-old in an area with a high incidence of tuberculosis. Respir Med. 2010 Aug;104(8):1211-7. DISCLOSURES: No relevant relationships by Adam Adam No relevant relationships by Moses Bachan No relevant relationships by Chen Chao No relevant relationships by Zinobia Khan No relevant relationships by Milena Vukelic

POST COVID-19 RHEUMATIC and MUSCULOSKELETAL DISEASES

Background: Recent data suggests that SARS-Cov-2 can alter self-tolerance and trigger autoimmune responses through cross-reactivity with host cells;therefore it can lead to late autoimmune and infammatory manifestations. With regard to rheumatic and musculoskeletal diseases (RMDs), medical literature displays sporadic case reports describing a variety of conditions diagnosed after COVID-19, but it remains still unclear what are the most common problems in patients presenting to rheumatology clinic following COVID-19 disease. Objectives: To describe the pattern of post-COVID-19 RMDs in a consecutive group of patients from rheumatology outpatient clinic. Methods: We have performed an observational descriptive study of a group of adult patients who received a new diagnosis of RMD within a timeframe of 12 weeks after the confirmation of COVID-19. Data was collected based on clinical presentation, paraclinical pattern and radiological examinations. Results: The study included 23 patients who were consulted in rheumatology outpatient clinic and had post COVID-19 new onset joint, periarticular, bone or infammatory syndrome manifestations. The general characteristics of the study group were as follows: mean age 45.5±11.3 (range 21-63) years and female to male ratio of 1.8:1. The majority of subjects consulted for joint symptoms (91.4%), in other cases reason for consultation was persistent low grade fever and fatigue (4.3%) and skin rash with dyspnea (4.3%). The mean duration of symptoms was 9.8±10.5 (range 1-42) weeks, and the time of onset after COVID-19 diagnosis was 4.9±4.1 (range 0-12) weeks. Concerning COVID-19 severity, it was established that in 60.9% it was mild, 17.4 %-moderate and 21.7%-severe. After clinical and paraclinical examination, the following diseases were diagnosed: ReA, lupus like syndromes, avascular necrosis, new onset RA and new onset PsA. In 69.7% of patients were diagnosed with ReA, the clinical pattern being joint or periarticular involvement of the hand, knee and feet. In 13.0% cases patients had multisystemic involvement (myocarditis, pericarditis, skin rash, infammatory arthritis and/or low grade fever) and positive ANA and or dsDNA Ab, these cases were diagnosed as lupus like syndromes and followed a severe form of COVID-19. In 8.7% of patients who presented with non-infammatory hip pain, avascular necrosis was diagnosed, in both cases femoral head being the affected part. No be noted that patients with avascular necrosis had a severe form of COVID-19 disease and joint pain started later after COVID-19 diagnosis (10-12 weeks). In 4.3% of cases each, new onset RA and PsA were identifed. Conclusion: In the present study we have found that COVID-19 can be followed by a variety of RMDs. The most common symptom of patients presenting with RMD was joint pain. The most common disease was post-COVID ReA (69.7%). Avascular necrosis (8.7%) and lupus like syndromes (13.0%) were found in patients who experienced a severe form of COVID-19. More rarely, patients had new onset of rheumatoid arthritis (4.3%) or psoriatic arthritis (4.3%). Our findings suggest that during the COVID-19 recovery period patients might experience onset of RDMs;therefore, in the presence of joint symptoms or other manifestations suggesting an autoimmune disease, patients should be referred to a rheumatologist for careful clinical examination.

CULTURAL BARRIERS AND PANDEMIC RESTRICTIONS RESULT IN A DELAYED DIAGNOSIS OF DRUG INDUCED LUPUS (DIL) AND SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

CASE: A 58-year-old female with a history of hypertension, type 2 diabetes and hyperlipidemia presented with a two- week history of abdominal pain and fevers. Per the patient, family history was unremarkable, and she denied alcohol, tobacco, or recreational drug use. She denied recent travel or sexual activity and had moved to the U.S. in the 1970s from Cambodia. Medications included amlodipine, atorvastatin, dapagliflozin, lisinopril, metformin and sitagliptin. Physical exam was notable for bilateral axillary lymphadenopathy, hepatomegaly, and right sided abdominal tenderness. Laboratory data was notable for microcytic anemia, thrombocytopenia, and elevated transaminases, D-dimer, and C- reactive protein. Urinalysis demonstrated microscopic hematuria and proteinuria. Imaging showed diffuse lymphadenopathy and hepatomegaly. Autoimmune work-up was strongly positive for ANA, anti-histone, and anti DS DNA. Kidney biopsy was suggestive of glomerulonephritis. Liver biopsy was suggestive of drug induced liver injury or autoimmune hepatitis. A diagnosis of DIL and SLE was not reached until additional historical data from the patient's son was provided on hospital day 4;namely that the patient had a 30-lb unintentional weight loss, took unknown herbal supplements and had a daughter who passed away from complications of lupus. IMPACT/DISCUSSION: DIL is a rare adverse reaction to many drugs that generally manifests with mild systemic symptoms such as low-grade fevers, anorexia, and fatigue and rarely involves classic symptoms of SLE such as skin findings and major organ involvement. Notably, DIL can unmask clinically silent SLE and thereby lead to lupus like syndromes. This patient presented with mild symptoms and underwent an extensive workup due to missing key historical data which led to a delayed diagnosis. Due to COVID-19 restrictions on visitation, it was not until hospital day 4 when the patient's son visited that the team became aware of an unintentional 30-lb weight loss, unknown herbal supplement use, and a family history of SLE. The lack of such critical information stemmed from the fact that we did not ask about the use of supplements properly and never revisited it in a different manner. The patient did not share the cause of her daughter's passing as she was unaware of it, which may speak to cultural limitations in sharing health information among family members. It is imperative that as clinicians we constantly revisit the history and diversify our questions. A more complete history would optimize our workup and limit unnecessary testing, including blood draws and painful biopsies, which unfortunately occurred in this patient. CONCLUSION: A thorough history is important to achieving a timely diagnosis and to avoid excessive testing and procedures. Revisiting the history is necessary to finding key information and clinicians should consider incorporating available family members early in the diagnostic work up, especially if the diagnosis is unclear.

A Rare Case of Concurrent New-Onset Microscopic Polyangiitis and Thrombotic Thrombocytopenic Purpura in a 77-Year-Old Woman

Introduction: Microscopic polyangiits (MPA) is a rare ANCA-associated necrotizing vasculitis that affects the small vessels, often involving the lung or kidney. When presenting with diffuse alveolar hemorrhage, this disease warrants emergent treatment, often with plasma exchange. Here, we present a rare case of a patient presenting with alveolar hemorrhage in the setting of MPA and concurrent thrombotic thrombocytopenic purpura (TTP) with an extremely reduced ADAMTS13 activity. Case Report: A 77 y/o woman with HTN and PUD presented to outside facility with new onset anemia (Hb 6.3 g/dL). Positive Coombs test gave her a tentative diagnosis of hemolytic anemia, and she was transfused 2 U RBCs. Ten days later, she presented to our hospital with respiratory distress. Hb remained stable at 10.7 but had leukocytosis with WBC 22,000 with left shift, platelets 439. Vitals not consistent with sepsis though saturating 70-80% on room air. In the ED, she developed frank hemoptysis and was emergently intubated. CTA chest was negative for pulmonary embolus but demonstrated diffuse ground-glass opacities. COVID test negative. Bronchoscopy was consistent with diffuse alveolar hemorrhage (DAH), and she received tranexamic acid, crystalloids, 1 U RBCs. Suspicious for underlying vasculitic process, she was given pulse dose IV steroids (1 g methylprednisolone daily) and started plasma exchange. Creatinine on presentation was elevated at 1.77 but she continued to have adequate urine output and appropriate volume status. Her hospital course was marked by progressive thrombocytopenia with schistocytes appreciated on peripheral smear. ADAMTS13 activity <5% with inhibitor detected, consistent with TTP. Vasculitic workup revealed positive myeloperoxidase antibodies and p-ANCA consistent with MPA. Other rheumatologic workup ANA positive 1:640 and positive IgM cardiolipin antibodies;she had no personal autoimmune history but some family autoimmune disease including one daughter with systemic lupus erythematosus and another relative with Guillian-Barre. She remained intubated for 4 days and post-extubation experienced some short-lived ICU delirium but after made a remarkable recovery. She completed 12 total sessions of of plasma exchange and 3 of 4 planned doses of rituximab, to continue on oral steroids outpatient and prophylactic TMP-SMX. She was discharged to rehab facility on hospital day 20. Discussion: With diffuse alveolar hemorrhage on presentation, initial differential remained broad including delayed presentation of transfusion-related lung injury (TRALI) given recent history of transfusion. She had recently started hydralazine outpatient. Along with positive ANA, this could suggest drug-induced lupus. However, histone antibodies were negative, but results may have been compromised by steroids and plasma exchange. Both MPA and TTP can be deadly but are managed with similar treatment. Luckily, our patient was rapidly initiated on plasma exchange following hospitalization. Although further workup including ADAMTS13 and vasculitis labs were pending at the time, it is important to not delay treatment while awaiting results. Cased of concurrent TTP and ANCA-associated vasculitis have been described in the literature, but the full relationship between these two entities remains unclear. TTP may develop after starting glucocorticoids in the setting of ANCA vasculitis, so close monitoring is recommended. Disclosures: No relevant conflicts of interest to declare.

Clinical manifestations of COVID-19 concerning the rheumatlogist

Over the last year, the concept of coronavirus disease 2019 (COVID-19) has undergone a major shift. Our initial understanding of COVID-19 as a flu-like illness was rethought as a polysyndromic inflammatory disease involving not only the respiratory system but also the musculoskeletal system, the skin, the cardiovascular system, and the genitourinary system. Within this inflammatory condition, the tissue damage is immunemediated, resembling the exacerbations of a full-blown rheumatic disease. Our aim was to describe the frequency and type of rheumatic manifestations in a cohort of patients with COVID-19 hospitalized in the Rheumatology Department for COVID-19 at Sv. Marina University Hospital, Varna, Bulgaria. In the current single-center cohort study, a retrospective database analysis was performed among all COVID-19 patients hospitalized from 1 December 2020 to 22 January 2021. All 243 patients (aged 19-93 years) were treated for moderate or severe SARS-CoV-2 infection confirmed by laboratory tests, including a positive polymerase chain reaction (PCR) test and imaging. Inpatient treatment includes dexamethasone, anticoagulants, antibiotics and the antiviral drug remdesevir (at clinical judgment). A detailed medical history and clinical examination were performed by a rheumatologist and/or internal medicine specialist. Among all 243 patients with COVID-19, those with a history of myalgia and arthralgia were 26% (n = 63) and 21.3% (n = 52), respectively. We found 4 (1.6%) cases of emerging cutaneous vasculitis and 2 (0.8%) cases of severe Raynaud's phenomenon after the onset of SARS-CoV-2 infection. Two patients had severe muscle weakness, elevated creatine phosphokinase, and were diagnosed with inflammatory myopathy caused by COVID-19. Lupus-like syndrome was observed in 2 (0.8%) patients. Rheumatic manifestations are part of the heterogeneous spectrum of COVID-19 disease. Amidst the COVID-19 pandemic, any newly onset rheumatic manifestation requires the exclusion of SARS-CoV-2 infection. Therefore, the rheumatologist should be a part of a multidisciplinary approach to the treatment of COVID-19.

A rare case of anti-tnf induced panniculitis

Case report-IntroductionPanniculitides comprise a heterogeneous group of inflammatory diseases involving the subcutaneous fat. They remain the most challenging areas for clinicians. Skin biopsy is commonly needed to confirm diagnosis. Because there are many underlying aetiologies for panniculitis, detailed history and thorough investigations are needed. We present a case of A 20-year male who was admitted with painful lumps treated initially as cellulitis/abscess but turned to be neutrophilic panniculitis on skin biopsy. Extensive workup failed to reveal underlying aetiology. Eventually Imradli (AntiTNF) was thought to be the culprit and therefore was kept on hold with no recurrence of panniculitis.Case report-Case descriptionA 20-year-old, Asian Malawian. Moved to the UK at the age of 6. He was diagnosed with Ankylosing spondylitis in November 2016. Initially received Naproxen followed by (Humira) with good clinical response. He was switched to biosimilar Imradli in Nov 2019. He was admitted with 2-3 weeks history of progressive right hip and buttock pain, 1 week of very tender erythematous swelling of the right buttock but without fever or weight loss. He reported mild weakness of lower limbs. Physical examination revealed 5x 8 cm swelling on Right buttock, Rest of examination was unremarkable. He was reviewed by neurology team who arranged MRI spine and brain, EMG and lumbar puncture which all came back as unremarkable excluding the possibilities of myelitis and myositis. Initially thought to be abscess/cellulitis but absence of fever/inflammatory response, abnormal CT finding and no response to antibiotics made it less likely. While the Right buttock erythema/swelling started to resolve, he developed two new migratory erythematous lesions appearing around the left buttock and lower lumbar spine. Working diagnosis of panniculitis was made which was confirmed on biopsy. Due to lack of response to NSAIDs, colchicine or oral steroids, a 3rd biopsy of the freshest lesion was performed to exclude deep-seated infection.Investigations-FBC, U&ES, LFT, CRP, CK, ACE-all were unremarkableASO titre <200, serology for Borrelia and TPHA negative.Viral, parasitic, and Autoimmune screen were unremarkable.CXR clear, MRI/CT: extensive subcutaneous inflammatory changes in the right buttock with sacral oedema.PET-CT-showed resolving inflammatory changes in the right flank, FDG intake in C6 and SI joints presumed secondary to ankylosing spondylitis and sacroiliitis.The underlying cause of panniculitis remains uncertain. Anti TNF was kept on hold and the patient was followed up with no evidence of recurrence of panniculitisCase report-DiscussionPanniculitis (inflammation of subcutaneous fat) is a relatively uncommon condition. It has various aetiologies including infection, trauma, inflammation, and malignancy. Skin biopsy can give valuable information including microbiological studies if infectious panniculitis was suspected. However, clinical correlation and careful consideration of the differential diagnosis is needed in many cases.The diagnosis can be quite challenging as in this case where all investigations and skin biopsy could not point towards the underlying aetiology. Although anti-TNF inhibitors are commonly used in treating a wide range of autoimmune conditions. But their use can lead to the development of secondary autoimmune diseases, such as cutaneous vasculitis, lupus-like syndrome, and interstitial lung disease, paradoxically induced by anti-TNF-a agents. Llamas-Velasco and Requena, reported the first case of panniculitis induced by etanercept injection in a 62-year-old woman with severe psoriasis who developed an erythematous, slightly painful nodule on the skin of the anterior abdominal wall.Adalimumab induced lupus panniculitis was reported in a Rhu-lupus patient. Although the lesions stopped progressing after cessation of adalimumab, they remained unchanged for two more years. The mechanism for adalimumab-induced CLE is uncertain.Although there is not enough data about autoimmunity with biosimilars, we think seco dary autoimmune conditions could similarly be induced by biosimilar as illustrated in this case. Anti-TNF induced cutaneous panniculitis is considered most likely although uncertain. If anti-TNF drug-induced, this should gradually resolve but can be slow (4-6 months). Corticosteroids have been added for an anti-inflammatory response, but there was little benefit which might point to a different pathogenetic mechanism.NSAIDs has helped to keep his AS relatively stable during the COVID-19pandemic. During the last review, the patient expressed his wishes to go back on biologic. But the question remains whether he will a have a recurrence of panniculitis or not?Case report-Key learning points1/Anti-TNF inhibitors sometimes cause secondary autoimmune conditions like cutaneous vasculitis, lupus-like syndrome, but there is not enough data regarding biosimilar induced autoimmunity.2/This case illustrates the high importance of having a tissue diagnosis. (whenever there is an issue, the diagnosis would be in the tissue).3/There is still uncertainty whether a recurrence of panniculitis might occur or not if the patient went again on biologics.