Whats' happening on the follicular unit of adolescents after the COVID-19 pandemic: Severe acne is a growing problem of nowadays

Objectives: Acne is a leading skin problem in adolescents. After the end of COVID-19 pandemic, with the gradual transition to the routine life, we started to encounter more severe forms of acne in the last 6-month than we had seen before in the 10 year period of our Paediatric Dermatology outpatient clinic. Method(s): We evaluated the demographic and clinical characteristics, COVID infection and vaccination status, and treatment of patients who were treated at our Paediatric Dermatology outpatient clinic in the last 6 months due to severe acne. Result(s): One of our patients had acne fulminans, and four patients had acne conglobata. The common features of these patients presenting with severe acne were that they were young boys aged 15- 16 years, medium height, normal weight, and skin type 3-4. All patients had a family history of acne in their parents. They had no known comorbidities, additional treatment, history of nutritional supplement use, or accompanying arthralgia or arthritis. Four patients were initially treated with isotretinoin for severe acne, developed acne conglobata, and one developed acne fulminans during the follow-up period. Dapsone therapy was initiated in all patients according to the severity of the lesions, and adalimumab was administered to acne fulminans. Discussion(s): The frequent occurrence of severe forms of acne after the pandemic raises the question of whether COVID-19 infection or vaccination may play a role in its aetiology. Cases of mask-related acne exacerbation during COVID-19 have been well-described in the literature. However, there are no data on the effects of COVID-19 vaccination or infection on the development of severe acne. In this report, we present cases of adolescent patients with severe acne to investigate the possible reasons for the increasing number of severe acne cases presenting to our outpatient clinic during the postpandemic period.

Versatile Use of Mycobacterium indicus pranii (MIP) Vaccine

Mycobacterium indicus pranii (MIP) earlier known as Mw is a soil-borne, non-pathogenic, saprophytic and rapidly growing strain of mycobacteria. MIP is approved as a vaccine/ immunomodulator for various indications including mycobacterium infections like leprosy in humans. Its administration has resulted in satisfactory clinical improvement, accelerated bacillary clearance, and increased immune responses to Mycobacterium leprae antigens, thereby shortening the full recovery time of the patients. It also shares its antigens with M.tuberculosis. In the last decade, RCTs have been done establishing immunotherapeutic properties of MIP in the treatment of leprosy, tuberculosis, warts and experimently in leishmaniasis. Through its immune inducing and cytotoxic property, it has also proved beneficial for human use especially in treating lung cancer. The beneficial role of it is also being explored in breast, cervical, oral, liver, and bladder cancers. Various studies on MIP have shown that it has immune-modulating properties in humans. The curiosity of the human mind has led to it being tried in Covid treatment trials. The results have shown that administering MIP has lowered inflammatory markers in Covid 19 patients, promising us for it to be a potential treatment option. More RCTs with a larger sample size should be done to establish this. Cytokine storm seen in bacterial sepsis is also decreased with MIP administration. Considering the encouraging results in hastening recovery in various diseases it appears that MIP is perhaps not being exploited to its fullest potential. © 2023, Hind Kusht Nivaran Sangh (Indian Leprosy Association). All rights reserved.

Severe epidermolysis bullosa acquisita in a patient with graft-versus-host disease: causal or coincidental?

Graft-versus-host disease (GvHD) is common after haematopoietic cell transplantation (HCT). Mucocutaneous manifestations are variable and may simulate autoimmune bullous dermatoses. However, the association of GvHD with autoimmune disorders, including bullous dermatoses, is also well recognized. We describe a patient with GvHD in whom severe and relapsing epidermolysis bullosa acquisita (EBA) was diagnosed 3 years after transplant and propose a causal association with GvHD. A 66-year-old woman developed GvHD following allogeneic HCT for acute myeloid leukaemia in 2016. This affected her gastrointestinal tract and skin but improved with oral corticosteroids and ciclosporin. In 2019 she presented with a widespread rash consisting of large, tense, haemorrhagic blisters. Histological features were in keeping with EBA. Direct immunofluorescence was also consistent with EBA, demonstrating linear positivity for IgG and C3 confined to the blister base, as was detection of collagen VII antibodies on indirect immunofluorescence. She was admitted and treated with high-dose oral steroids, ciclosporin and intravenous immunoglobulin (IVIg) with eventual resolution of blistering. Although further IVIg administration was planned as an outpatient, this coincided with the start of the COVID-19 pandemic and she elected not to attend and also stopped all medication. Despite this, her EBA remained quiescent until September 2021 when she was readmitted with a severe deterioration in blistering and significant dysphagia due to an oesophageal stricture, with a weight of 31.7 kg. Once again, she responded rapidly to oral prednisolone and IVIg. Dapsone was considered but precluded by G6PD deficiency and there were clinical and adherence concerns about using mycophenolate mofetil. Upon discharge she was again nonadherent to medication and failed to attend for planned IVIg. She flared and was admitted for a third time in December 2021, requiring gastrostomy for nutritional support;her weight at this time was 26.4 kg. Her EBA is currently well controlled on prednisolone and IVIg. EBA is a rare, acquired blistering disorder secondary to autoantibodies targeting type VII collagen. Previous studies have found circulating basement membrane zone (BMZ) antibodies in 24% of chronic GvHD patients, possibly generated in response to chronic BMZ damage (Hofmann SC, Kopp G, Gall C et al. Basement membrane antibodies in sera of haematopoietic cell recipients are associated with graft-versushost disease. J Eur Acad Dermatol Venereol 2010;24: 587-94). Corresponding clinical manifestations are rare, with bullous pemphigoid the most frequently reported. EBA is much less common with four previously reported cases [Brassat S, Fleury J, Camus M, et al. (Epidermolysa bullosa acquisita and graftversus- host disease). Ann Dermatol Venereol 2014;141: 369-73 (in French)]. As a fifth case of EBA, our patient provides further evidence of a likely pathophysiological relationship between GvHD and autoimmune subepidermal bullous dermatoses, and highlights the significant challenges of managing these vulnerable patient groups during the COVID-19 pandemic.

The Potential Effect of Dapsone on the Inflammatory Reactions in Covid-19: Staggering view.

Severe SARS-CoV-2 infection is linked with an overstated immune response with the succeeding release of pro-inflammatory cytokines and progression of the cytokine storm. In addition, severe SARS-CoV-2 infection is associated with the development of oxidative stress and coagulopathy. Dapsone (DPS) is a bacteriostatic antibiotic that has a potent anti-inflammatory effect. Thus, this mini-review aimed to elucidate the potential role of DPS in mitigating inflammatory disorders in Covid-19 patients. DPS inhibits neutrophil myeloperoxidase, inflammation, and neutrophil chemotaxis. Therefore, DPS could be effective against neutrophilia-induced complications in Covid-19. In addition, DPS could be effective in mitigating inflammatory and oxidative stress disorders by suppressing the expression of inflammatory signaling pathways and the generation of reactive oxygen species (ROS) correspondingly. In conclusion, DPS might be effective in the management of Covid-19 through the attenuation of inflammatory disorders. Therefore, preclinical and clinical studies are reasonable in this regard.

Dapsone Lowers Neutrophil to Lymphocyte Ratio and Mortality in COVID-19 Patients Admitted to the ICU.

Some physicians use dapsone as part of the standard treatment of severe COVID-19 patients entering the ICU, though some do not. To obtain an indication of whether dapsone is helping or not, we undertook a retrospective chart review of 29 consecutive ICU COVID-19 patients receiving dapsone and 30 not receiving dapsone. As we previously reported, of those given dapsone, 9/29 (30%) died, while of those not given dapsone, 18/30 (60%) died. We looked back on that data set to determine if there might be basic laboratory findings in these patients that might give an indication of a mechanism by which dapsone was acting. We found that the neutrophil-to-lymphocyte ratio decreased in 48% of those given dapsone and in 30% of those not given dapsone. We concluded that dapsone might be lowering that ratio. We then reviewed collected data on neutrophil related inflammation pathways on which dapsone might act as presented here. As this was not a controlled study, many variables prevent drawing any conclusions from this work; a formal, randomized controlled study of dapsone in severe COVID-19 is warranted.

COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated type 1 interferon (IFN-1) production, the pathophysiology of which involves sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) tetramerization and the cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. As a result, type I interferonopathies are exacerbated. Aspirin inhibits cGAS-mediated signaling through cGAS acetylation. Acetylation contributes to cGAS activity control and activates IFN-1 production and nuclear factor-κB (NF-κB) signaling via STING. Aspirin and dapsone inhibit the activation of both IFN-1 and NF-κB by targeting cGAS. We define these as anticatalytic mechanisms. It is necessary to alleviate the pathologic course and take the lag time of the odds of achieving viral clearance by day 7 to coordinate innate or adaptive immune cell reactions.

REFRACTORY HYPOXEMIA: A CASE OF DAPSONE-INDUCED METHEMOGLOBINEMIA IN A PATIENT WITH COVID-19

SESSION TITLE: Drug-Induced and Associated Critical Care Cases Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Methemoglobinemia is an increase in methemoglobin (mHb) level characterized by functional anemia and tissue hypoxia. It can be caused by congenital enzymes deficiencies, but it is usually acquired. Dapsone, an oxidizing agent, is a medication commonly associated with acquired methemoglobinemia (1). We describe the diagnosis and management of a COVID-19 patient with acquired methemoglobinemia due to Dapsone. CASE PRESENTATION: 84-year-old female with history of MPO-ANCA vasculitis with renal involvement, CKD4 and anemia of chronic disease presented with shortness of breath, lethargy and weakness. Initially, the patient was saturating (SpO2) 80% on room air and was placed on 4L nasal cannula (NC) with improvement to 92%. CT of the chest showed b/l GGOs consistent with atypical pneumonia and patient tested positive for COVID-19. About 4 months prior, she had received 2 doses of Rituximab and on high steroid therapy that was tapered to 5mg of prednisone daily. She has been on Trimethoprim/Sulfamethoxazole for PJP prophylaxis, but due to hyperkalemia the medication was stopped. After confirming no G6PD deficiency, she was started on Dapsone 100mg daily. During hospitalization, she was given dexamethasone 6 mg daily and Dapsone was continued. On hospital stay day 6, a rapid response was called after oxygen dropped to 78% while walking on 6L NC. She was placed on high flow NC 100% and SpO2 went up to 90%. An arterial blood gas (ABG) was then obtained showing pO2 of 334, oxyhemoglobin (oxyHb) of 83 and mHb of 17.4. The SpO2-PaO2 gap and elevated mHb lead to the diagnosis of Dapsone-induced methemoglobinemia. Dapsone was discontinued. Patient received a one-time dose of 1mg/kg IV of methylene blue. One hour later her dyspnea had improved and was on 3L NC. Repeat ABG showed improvement of oxyHb (98) and decreased mHb (2.2). DISCUSSION: Physiologically, mHb is less than 1% of total Hb (1) and occurs when the iron in the porphyrin group of heme is oxidized from ferrous to the ferric form (2). Ferric heme binds oxygen irreversibly causing a left shift of the oxygen-hemoglobin dissociation curve. Clinical presentation tends to correlate with mHb levels, and it varies from being asymptomatic to fatigue, dyspnea, confusion, seizure, cyanosis resistant to oxygen therapy (mHb > 15%) and death. Methylene blue is safe and can be consider when mHb level is greater than 10 to 20% (2). Methylene blue was administer to our patient given the presence of COVID (leaving patient more susceptible to medication-induced methemoglobinemia (3)) and chronic anemia which made her less likely to tolerate state of reduced oxygen delivery. CONCLUSIONS: The diagnosis of methemoglobinemia is a rare cause of hypoxemia that is often overlooked. In patients with risk factors (COVID, medication exposure) a high index of suspicion is needed when interpreting an ABG (SpO2-PaO2 gap) for correct diagnosis and appropriate treatment. Reference #1: Toker, Ibrahim, et al. "Methemoglobinemia Caused by Dapsone Overdose: Which Treatment Is Best?” Turkish Journal of Emergency Medicine, vol. 15, no. 4, Dec. 2015, pp. 182–184, 10.1016/j.tjem.2014.09.002. Accessed 31 Aug. 2020. Reference #2: Cortazzo JA, Lichtman AD. Methemoglobinemia: a review and recommendations for management. J Cardiothorac Vasc Anesth. 2014 Aug;28(4):1043-7. doi: 10.1053/j.jvca.2013.02.005. Epub 2013 Aug 13. PMID: 23953868. Reference #3: Naymagon, Leonard, et al. "The Emergence of Methemoglobinemia amidst the COVID -19 Pandemic.” American Journal of Hematology, vol. 95, no. 8, 3 June 2020, 10.1002/ajh.25868. Accessed 3 Mar. 2021. DISCLOSURES: No relevant relationships by Mileydis Alonso No relevant relationships by Samantha Gillenwater No relevant relationships by Christine Girard No relevant relationships by Sikandar Khan No relevant relationships by Jose Rivera No relevant relationships by Frederick Ross

DAPSONE-INDUCED METHEMOGLOBINEMIA IN COVID-19: A MIMIC OF “HAPPY HYPOXIA”

SESSION TITLE: Drug-Induced Lung Injury and Disease SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: COVID-19 has been notorious to cause "happy hypoxia” or presentation with profound hypoxia yet without proportional signs of respiratory distress. Methemoglobinemia is a rare and potentially life threatening condition characterized by an inability of hemoglobin to bind oxygen leading to diffuse tissue hypoxia. Diagnosis of methemoglobinemia in a patient with COVID-19 may be masked if the index of suspicion is low. We present such case of dapsone-induced methemoglobinemia in the setting of COVID-19. CASE PRESENTATION: A 64-year-old male presented to the hospital with fatigue. His past medical history included Type 1 Diabetes Mellitus (DM), hypertension and dermatitis herpetiformis. He also reported a 6 day history of testing positive for COVID-19 as an outpatient. His initial vital signs were stable and his peripheral oximeter showed a 96% saturation on 2L O2. Physical exam was unremarkable without any signs of respiratory distress. His labs were notable for blood glucose of 500, high anion gap metabolic acidosis concerning for diabetic ketoacidosis (DKA). A chest X-ray (CXR) revealed bilateral infiltrates. He was initiated on insulin drip and per hospital protocol initiated on Remdesevir and Decadron for COVID-19 treatment. Patient's DKA subsequently resolved. However on Day 4, patient's oxygen saturation decreased suddenly to the 80s without any signs of respiratory distress. Infectious workup including CBC, sputum culture, antigen for streptococcus, legionella returned negative. His CXR remained unchanged. Arterial blood gas (ABG) demonstrated pH of 7.45, pCo2 46mm Hg, pO2 157 mm Hg. Methemoglobin level was found to be 14.1%. He was given methylene blue 1 mg/kg and dapsone was discontinued. His methemoglobin level improved to 3.4% the next day. He was subsequently discharged home without need for supplemental oxygen. DISCUSSION: Methemoglobinemia can be acquired through drugs that oxidize the ferrous hemoglobin to ferric form. Dapsone is one such agent commonly used for dermatological conditions and opportunistic infection prophylaxis. The oxidative stress caused due to COVID-19 coupled with Dapsone use may have precipitated methemoglobinemia in our patient. Since the presentation can easily mimic "happy hypoxia", index of suspicion for methemoglobinemia can be low and thus can have profound consequences if undetected and not treated. CONCLUSIONS: In the setting of COVID-19 pneumonia with refractory hypoxemia, clinicians should have a high index of suspicion for methemoglobinemia especially in patients on highly oxidative medications. Reference #1: Burke P, et al. Dapsone-induced methemoglobinemia: case of the blue lady. Can Fam Physician. 2013 Sep;59(9):958-61. Reference #2: Naymagon L., Berwick S., Kessler A., et al. The emergence of methemoglobinemia amidst the COVID-19 pandemic. Am. J. Hematol. 2020;95: E196-E197 https://doi.org/10.1002/ajh.25868 Reference #3: Faisal H, Bloom A, Gaber AO. Unexplained Methemoglobinemia in Coronavirus Disease 2019: A Case Report. A&A Pract. 2020;14(9):e01287. doi:10.1213/XAA.0000000000001287 DISCLOSURES: No relevant relationships by Syed Azharuddin Speaker/Speaker's Bureau relationship with gsk Please note: 2020-present by Tariq Cheema, value=Honoraria Speaker/Speaker's Bureau relationship with GSK Please note: 2020 Added 04/14/2022 by Tariq Cheema, value=Honoraria Removed 04/14/2022 by Tariq Cheema Speaker/Speaker's Bureau relationship with BI Please note: 2020-PRESENT Added 04/14/2022 by Tariq Cheema, value=Honoraria Speaker/Speaker's Bureau relationship with astra zeneca Please note: 2020-Present Added 04/14/2022 by Tariq Cheema, value=Honoraria Speaker/Speaker's Bureau relationship with regeneron Please note: 2021-Present Added 04/14/2022 by Tariq Cheema, value=Honoraria No relevant relationships by Deeksha Ramanujam No relevant relationships by Alisha Sharma

A CASE OF PNEUMOCYSTIS JIROVECI PNEUMONIA MIMICKING METHOTREXATE-INDUCED PNEUMONITIS

SESSION TITLE: Procedures in Chest Infections Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Pneumocystis jirovecii pneumonia (PJP) is known to cause potentially life-threatening pneumonia in patients on immunosuppressive therapy. Here we describe a case of an elderly man on low dose methotrexate with PJP pneumonia initially mistaken for drug induced pneumonitis. CASE PRESENTATION: A 79 year old man with T-cell large granular lymphocytic leukemia on methotrexate, indeterminate colitis on azathioprine and sulfasalazine and interstitial lung disease was admitted for 3 week history of worsening dyspnea, lethargy and cough. On arrival his oxygen saturation was 87% on room air, requiring 5 liters oxygen via nasal canula. Lung examination was notable for bilateral crackles. Laboratory studies showed white blood cell count 12.4k/μL, lactate 2.7mmol/L, procalcitonin 0.137ng/mL, lactate dehydrogenase(LDH) 925 IU/L, 1,3 β-D glucan elevated at 154pg/mL. Infectious work up including COVID-19 testing was unremarkable. Chest radiograph showed bilateral diffuse interstitial infiltrates (figure 1) and computed tomography (CT) scan showed peripheral reticular changes and patchy ground glass opacities bilaterally (figures 2;3). He was initially treated for possible bacterial pneumonia;then with 125mg of methylprednisolone for presumed methotrexate induced pneumonitis without improvement. He underwent bronchoscopy with bronchoalveolar lavage(BAL) gram stain showing numerous histiocytes and scattered lymphocytes;no infectious organisms were isolated. PJP PCR from BAL came back positive and trimethoprim-sulfamethoxazole (TMP-SMX) was started. Despite maximum therapy he deteriorated clinically, transitioned to comfort care and expired. DISCUSSION: Diagnosis of PJP is made by visualization of cystic or trophic forms in respiratory tissue obtained via biopsy, BAL or sputum. Fungal burden is typically lower in non-HIV patients with PJP, and may result in negative BAL or sputum stain. Thus PCR testing is a useful diagnostic tool. Positive PCR alone cannot distinguish between colonization and active disease, and should be performed when clinical suspicion is high. 1,3 β-D glucan and LDH are nonspecific markers that help in presumptive diagnosis. First line therapy for PJP is TMP-SMX, with atovaquone, dapsone and pentamidine available as alternative therapies. Duration of therapy should be at least 21 days. Adjunctive corticosteroids show survival benefit in HIV-infected individuals. In severely hypoxic patients, corticosteroids are beneficial if started within 72 hours of antibiotic initiation. Their use in non-HIV PJP cases remains controversial. CONCLUSIONS: This case highlights the risk of PJP with long term methotrexate therapy. Cough, hypoxemia and bilateral interstitial infiltrates should prompt work-up for PJP. Timely recognition and early treatment are crucial to prevent mortality. Further studies are needed to assess the efficacy and provide guidelines for primary prophylaxis in this population. Reference #1: Wilson JW, Limper AH, Grys TE, Karre T, Wengenack NL, Binnicker MJ. Pneumocystis jirovecii testing by real-time polymerase chain reaction and direct examination among immunocompetent and immunosuppressed patient groups and correlation to disease specificity. Diagn Microbiol Infect Dis. 2011 Feb;69(2):145-52. doi: 10.1016/j.diagmicrobio.2010.10.021. PMID: 21251557;PMCID: PMC6855182. Reference #2: Salzer HJF, Schäfer G, Hoenigl M, Günther G, Hoffmann C, Kalsdorf B, Alanio A, Lange C. Clinical, Diagnostic, and Treatment Disparities between HIV-Infected and Non-HIV-Infected Immunocompromised Patients with Pneumocystis jirovecii Pneumonia. Respiration. 2018;96(1):52-65. doi: 10.1159/000487713. Epub 2018 Apr 10. PMID: 29635251 DISCLOSURES: No relevant relationships by Rutendo Jokomo-Nyakabau No relevant relationships by Richard Swaney No relevant relationships by Manasa Velagapudi

PROSPECTIVE OBSERVATIONAL STUDY IN PATIENTS WITH IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP) TREATED WITH TPO-R AGONISTS (TPO-RA): ELTROMBOPAG (EPAG) AND ROMIPLOSTIM (ROMI) - THE PEPITE STUDY

Background: Initially, the marketing authorization (MA) of EPAG and ROMI was to adult patients (p.) with ITP ≥12 months (m.) and refractory to other treatments (t.), splenectomized or contraindicated to splenectomy. The MA was extended for EPAG in 2019 to p. aged ≥1 year with ITP ≥6 m., refractory to other t. (corticoids (CS), IgIV). In 2017, French national guidelines suggested the use of TPO-RA as an option of t. in 2nd line (L). Aims: The PEPITE study, still ongoing, aims to assess the modalities of use, effectiveness and safety of TPO-RAs in reallife. Methods: Prospective, observational, multicenter study including adult p. who initiated TPO-RA with persistent (pITP) or chronic (cITP) ITP. Inclusions occurred between 12/21/2018 and 07/17/2020. Here's the interim analysis, cut-off date: 03/22/2021. Characteristics at baseline were presented in 114 p. (analyzed pop). Efficacy analysis of TPO-RA was assessed in p. with a platelet count (PLAT) <100 G/L at TPO-RA initiation (efficacy pop 113 p.). Responses were defined as: response (R) = PLAT ≥30 G/L, complete response (CR) = PLAT ≥100 G/L and non-response (NR) = PLAT <30 G/L. Results: 123 p. included through 40 centers by 25 hematologists and 15 internists, and 77 p. were still on TPO-RA at 6 m. At baseline, mean age 62.7 ± 20.1 years, 55% men, 29% with at least 1 cardiovascular risk factor. At diagnosis: median PLAT = 26 G/L [0 to 134 G/L], 31% of p. with bleedings. 97% of p. received at least one L of t. before TPO-RA: CS 96%, IVIG 56%, rituximab 47%, dapsone 18%, hydroxychloroquine 11%, danazol 6% and 7% of p. were splenectomized. Median number L of t. = 2 and 8% of p. had more than 4 L. Median time between diagnosis and TPO-RA initiation was 2.6 years [0.3 to 49.3 years], 33% of p. with pITP (n=21 with ITP 3 -<6 months, n=16 with ITP 6 - <12 months) and 67% with cITP. At TPO-RA initiation: 9% of p. were on CS and 48% p. had PLAT <30 G/L (median PLAT = 30 G/L), 95 p. (83%) received EPAG and 19 p. (17%) ROMI. For the 77 p. still on TPO-RA at 6 m., R rate = 97% and CR = 60%. Within 6 m., 10 p. had permanently (perm.) discontinued TPO-RA, main causes were therapeutic effect deemed sufficient (TEDS) for 6 p. and NR for 2 p. For the 27 p. still treated with TPO-RA at 18 m., R rate = 93% and CR = 48%. Within 18 m., 12 p. had perm. stopped TPO-RA, including 7 p. for TEDS and 1 p. NR. P. initiated TPO-RA with ITP 3 -<6 months (N = 21), 9 (43%) p. were still on TPO-RA at 6 months, 5 (56%) in CR. Over the entire follow-up, 24p. (21%) perm. discontinued TPO-RA, main causes were TEDS for 9 p., adverse event (AE) for 5 p. and absence of R for 4 p. Of the 105 p. treated with EPAG at least once, 62 (59%) experienced at least one AE, and 26 SAE occurred in 17 p. The most common AEs were respectively 6% for headache and 3% for SARS-CoV-2 infections, diarrhea, asthenia, insomnia, arthralgia and alopecia. Of the 40 p. treated with ROMI at least once, 19 (48%) experienced at least one AE and 17 SAEs occurred in 10 p. The most common AEs: SARS-CoV-2 infections (5%) and arthralgias (5%). No deaths related to TPO-RA was reported. Summary/Conclusion: Preliminary data from the PEPITE study show that TPO-RA are prescribed in early ITP, including 33% with pITP (18% with ITP 3-<6 m.) and are used in 7% of cases after splenectomy. At 6 m. R on t. was 97% and CR on t. was 60%. Within 6 m., 6 p. had perm. stopped TPO-RA due to TEDS. The real-life effectiveness and safety data for EPAG and ROMI are consistent with data reported in extension studies, with the specificity of occurrence of SARS-CoV-2. The final analysis is scheduled after 24 m.

A case of successful management of adult-onset linear IgA bullous disease with sulfasalazine during the COVID-19 pandemic

Linear IgA bullous disease (LABD) is a rare, acquired, autoimmune, pruritic and blistering skin condition. Dapsone is a first line treatment option, however there are limited options if this fails, or was contraindicated. We present a case of successful management of LABD with sulfasalazine. A 46-year-old white woman with LABD was commenced on high-dose corticosteroids. She failed weaning, and dapsone was contraindicated due to a history of primary sclerosing cholangitis and risk of hepatitis. Following the failure of mycophenolate mofetil, sulfasalazine was trialled, and successfully controlled both the patient's LABD and ulcerative colitis. There is little literature on the use of sulfasalazine in dermatological conditions. We present sulfasalazine as an option for patients who are unable to tolerate classically used treatments for LABD, or in those who have a dual diagnosis, as in this case, allowing for one agent to manage both conditions. Furthermore, the National Institute for Health and Care Excellence (NICE) guidance mentions sulfasalazine as one of the few drugs that can be continued during the COVID-19 pandemic, and its use spared this patient from the significant immunosuppression associated with other treatment modalities.

SARS-CoV-2 infection, pulse oximetry, and interpretive caveats.

Hypoxaemia in COVID-19 does not necessarily imply COVID pneumonia or post-COVID lung fibrosis, and the caveats of finger pulse oximetry should be remembered. Drug-induced methaemoglobinemia should be considered in individuals with unexplained cyanosis, refractory hypoxaemia, or the presence of a saturation gap. Here, we share our recent encounter of 'spurious hypoxia' in a patient with COVID-19 and methaemoglobinemia.

Untangling a rare case of hypoxia

Introduction: Hypoxia is a very common symptom during this COVID-19 pandemic. Detailed history, clinical examination and relevant investigations are important in distinguishing rare causes from commonest. Case Report: 52-year-old lady presented to emergency room with sudden onset breathlessness. She was recently diagnosed with Idiopathic Thrombocytopenic Purpura (ITP). She was found to be hypoxic with a room air saturation of 82% in pulse oximeter. She was started on high flow oxygen. But her saturation didn't improve. Chest X-ray showed normal lung fields and bedside echocardiography revealed normal cardiac status. Point of care blood gas analysis (ABG) revealed a normal partial pressure of oxygen (Pao2-100). The discrepancy between oxygen saturation recorded in pulse oximetry and PaO2 in blood gas analysis tempted us to relook the ABG. It was found that the methaemoglobin level in ABG was 10.7%. When we analysed her drug history, we found that there was dapsone intake for the treatment of ITP which strongly supported us to reach the diagnosis of methemoglobinemia. She was then treated with intravenous methylene blue in the emergency room. She responded well and her repeated ABG revealed normalized level of methaemoglobin. Her hypoxia also resolved. Dapsone was later removed from her regular medications. Conclusion: Methemoglobinemia is an extremely rare cause for hypoxia. Though rare its potentially life threatening if not identified on time. Refractory hypoxia with a discrepancy in spo2 and PaO2 should raise the suspicion of methemoglobinemia. IV methylene blue is the recommended treatment for methemoglobinemia.

Diagnosis and Treatment Challenges of an Atypical Case of Pemphigus vulgaris During the COVID-19 Pandemic.

Pemphigus defines a group of rare autoimmune blistering diseases that affect the skin and mucous membranes, with pemphigus vulgaris being the most common form that has increased morbidity and mortality in the absence of an early diagnosis and treatment. We report the case of a 24-year-old male with an atypical form of pemphigus vulgaris with cutaneous onset and subsequent involvement of the oral cavity. The management of the patient initially consisted of long-term systemic corticosteroid therapy. Following a mild form of SARS-CoV-2 infection and a flare-up of the disease in this context, which was not controlled with high doses of systemic corticosteroids, targeted therapy with rituximab was initiated but immediately stopped due to the manifestations of urticaria and angioedema. Considering the magnitude of these reactions, dapsone systemic therapy i.e., a steroid-sparing agent with minimal risk of infections, was started and managed to control the underlying disease. The management of this case of pemphigus vulgaris was challenging for both the patient and his physician, as the patient developed COVID-19 which caused disease complications and implied additional costs. This case highlights the importance of an accurate diagnosis given the atypical onset of the disease and the financial limitations with the impossibility of performing all confirmatory diagnostic tests.

Subcorneal pustular dermatosis with temporary autoimmune features during COVID-19 pandemic. (Special Issue: Coronavirus disease (COVID-19).)

Subcorneal pustular dermatosis, Sneddon-Wilkinson, is an uncommon neutrophilic dermatosis of unknown etiology. We report on a 51-year-old woman who presented with multiple superficial erythematous erosions surrounded by annular arranged sterile pustules concentrated on the trunk, the neck, and the proximal extremities during the coronavirus disease-19 pandemic. Larges pustules and flaccid bullae showed a hypopyon. There were no fever and no pruritus, general health was unaffected. Laboratory investigations revealed leukocytosis, neutrophilia, lymphopenia, and increased C-reactive protein. Initially, antinuclear antibodies, pemphigoid antibodies, and antibodies to BP 230 were positive, but negative 5 days later. Nasopharyngeal swabs were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA tested by real-time reverse-transcriptase-polymerase chain reaction. A diagnostic skin biopsy showed epidermal spongiotic vesiculation and subcorneal pustulation with acantholysis and an inflammatory infiltrate composed of neutrophils and lymphocytes. The confirmed diagnosis was subcorneal pustular dermatosis Sneddon-Wilkinson. She was treated by dapsone and corticosteroids with the latter tempered down. Clinical response was rapid. We suggest that the autoimmune features seen on admission may be due to an undefined viral infection, but not SARS-CoV-2.

Endometriosis Susceptibility to Dapsone-Hydroxylamine-Induced Alterations Can Be Prevented by Licorice Intake: In Vivo and In Vitro Study.

Endometriosis, an estrogen-dependent chronic gynecological disease, is characterized by a systemic inflammation that affects circulating red blood cells (RBC), by reducing anti-oxidant defenses. The aim of this study was to investigate the potential beneficial effects of licorice intake to protect RBCs from dapsone hydroxylamine (DDS-NHOH), a harmful metabolite of dapsone, commonly used in the treatment of many diseases. A control group (CG, n = 12) and a patient group (PG, n = 18) were treated with licorice extract (25 mg/day), for a week. Blood samples before (T0) and after (T1) treatment were analyzed for: i) band 3 tyrosine phosphorylation and high molecular weight aggregates; and ii) glutathionylation and carbonic anhydrase activity, in the presence or absence of adjunctive oxidative stress induced by DDS-NHOH. Results were correlated with plasma glycyrrhetinic acid (GA) concentrations, measured by HPLC-MS. Results showed that licorice intake decreased the level of DDS-NHOH-related oxidative alterations in RBCs, and the reduction was directly correlated with plasma GA concentration. In conclusion, in PG, the inability to counteract oxidative stress is a serious concern in the evaluation of therapeutic approaches. GA, by protecting RBC from oxidative assault, as in dapsone therapy, might be considered as a new potential tool for preventing further switching into severe endometriosis.

Benefits of Using Dapsone in Patients Hospitalized with COVID-19.

Since the start of the SARS-CoV-2 pandemic, refractory and relentless hypoxia as a consequence of exuberant lung inflammation and parenchymal damage remains the main cause of death. We have earlier reported results of the addition of dapsone in this population to the standard of care. We now report a further chart review of discharge outcomes among patients hospitalized for COVID-19. The 2 × 2 table analysis showed a lower risk of death or discharge to LTAC (Long term acute care) (RR = 0.52, 95% CI: 0.32 to 0.84) and a higher chance of discharge home (RR = 2.7, 95% CI: 1.2 to 5.9) among patients receiving dapsone compared to those receiving the usual standard of care. A larger, blinded randomized trial should be carried out urgently to determine if dapsone indeed improves outcomes in COVID-19.

Dapsone as treatment adjunct in ARDS.

Multiple pharmacological interventions tested over the last decades have failed to reduce ARDS mortality. This short note recounts past data indicating that (i) neutrophils home along an IL-8 gradient, (ii) in ARDS, massive neutrophil accumulation and degranulation in and along bronchoalveolar spaces contributes to damage and hypoxia, (iii) large increases in IL-8 are one of the chemotaxic signals drawing neutrophils to the ARDS lung, and (iv) old data from dermatology and glioblastoma research showed that the old drug against Hansen's disease, dapsone, inhibits neutrophils' chemotaxis to IL-8. Therefore dapsone might lower neutrophils' contributions to ARDS lung pathology. Dapsone can create methemoglobinemia that although rarely problematic it would be particularly undesirable in ARDS. The common antacid drug cimetidine lowers risk of dapsone related methemoglobinemia and should be given concomitantly.

4,4'-Diaminodiphenyl Sulfone (DDS) as an Inflammasome Competitor.

The aim of this study is to examine the use of an inflammasome competitor as a preventative agent. Coronaviruses have zoonotic potential due to the adaptability of their S protein to bind receptors of other species, most notably demonstrated by SARS-CoV. The binding of SARS-CoV-2 to TLR (Toll-like receptor) causes the release of pro-IL-1ß, which is cleaved by caspase-1, followed by the formation and activation of the inflammasome, which is a mediator of lung inflammation, fever, and fibrosis. The NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome is implicated in a variety of human diseases including Alzheimer's disease (AD), prion diseases, type 2 diabetes, and numerous infectious diseases. By examining the use of 4,4'-diaminodiphenyl sulfone (DDS) in the treatment of patients with Hansen's disease, also diagnosed as Alzheimer's disease, this study demonstrates the diverse mechanisms involved in the activation of inflammasomes. TLRs, due to genetic polymorphisms, can alter the immune response to a wide variety of microbial ligands, including viruses. In particular, TLR2Arg677Trp was reported to be exclusively present in Korean patients with lepromatous leprosy (LL). Previously, mutation of the intracellular domain of TLR2 has demonstrated its role in determining the susceptibility to LL, though LL was successfully treated using a combination of DDS with rifampicin and clofazimine. Of the three tested antibiotics, DDS was effective in the molecular regulation of NLRP3 inflammasome activators that are important in mild cognitive impairment (MCI), Parkinson's disease (PD), and AD. The specific targeting of NLRP3 itself or up-/downstream factors of the NLRP3 inflammasome by DDS may be responsible for its observed preventive effects, functioning as a competitor.