Dapsone: A Century-Old Medicine and a New Hope for Severe COVID-19

Background: The 2020 pandemic of COVID-19 infection, which has already lasted more than 22 months, is not subsiding. Despite the available vaccinations, the infection is still claiming many lives throughout the world, especially among the unvaccinated people. The newly discovered and fast spreading Omicron variant also raises the concern if vaccination alone will be sufficient to win this battle. Purpose: In this concept paper, we examine the possible use dapsone, a century-old and safe medication, to treat patients with severe cases of pulmonary COVID-19 infection. Methods: We aim to delineate the similarities between IgA-mediated neutrophil-directed blistering skin diseases and the severe pulmonary COVID-19 infection by reviewing the relevant medical literatures, in order to compare the pathological mechanisms of these two different clinical situations. Results: Analysis of published reports reveals strong evidence pointing to the involvement of IgA and neutrophils in both clinical situations. In addition, results of a small clinical trial showed efficacy of dapsone in patients suffered with severe COVID-19 infection. Conclusions: Since dapsone is effective in treating IgA-mediated skin diseases by blocking the binding of neutrophils to the tissue site, it could also be an effective treatment for severe cases of COVID-19 lung injury, which has a similar pathological mechanism.

Acute dapsone poisoning in a 3-year-old child: Case report with review of literature

Dapsone(DDS-diamino diphenyl sulphone) is a sulfone antibiotic being used for a variety of clinical conditions. Poisoning in children by DDS is rarely reported. Poisoning in acute cases will be frequently unrecognized due to relative lack of severe signs and symptoms. Methemoglobinemia is the major life-threatening situation associated with poisoning of DDS. Hence, any delay for medical attention can lead to increased rate of mortality. In this case, we describe acute DDS poisoning in a 3-year-old child and the successful management using intravenous methylene blue.

Psoriasis treatment: Unconventional and non-standard modalities in the era of biologics

Psoriasis is a potentially debilitating inflammatory dermatosis affecting 0.2%-4.8% of the population worldwide causing a significant occupational, personal or psychosocial morbidity to these patients for life. The basic aim of psoriasis therapy is to control the disease to maximum possible extent and improve the patient's quality of life. Management of triggers for flareups, lifestyle modifications, and dietary supplements are often recommended. Intermittent or rotational therapy with frequent alterations in treatment options is usually needed to reduce toxicity of anti-psoriatic drugs in the absence of safer alternatives. Currently, several biological agents categorized as either T-cell targeted(e.g., Alefacept, Efalizumab) or cytokine modulating(e.g., Adalimumab, Infliximab, Etanercept) are available for treating severe psoriasis. However, their high cost is often precluding for most patients. The usefulness of systemic(methotrexate, cyclosporine, acitretin or several other therapeutic agents) or topical(tar, anthralin, corticosteroids or calcipotriol ointments, phototherapy with or without psoralens) therapies has been well established for the management of psoriasis. The literature is also replete with benefits of less used non-standard and unconventional treatment modalities(hydroxycarbamide, azathioprine, leflunomide, mycophenolate mofetil, isotretinoin, fumarates, topical calcineurin inhibitors, peroxisome proliferator-activated receptors agonists, statins, sulfasalazine, pentoxifylline, colchicine, grenz ray therapy, excimer laser, climatotherapy and balneophototherapy, peritoneal dialysis, tonsillectomy, ichthyotherapy, etc.). These can be used alternatively to treat psoriasis patients who have mild/minimal lesions, are intolerant to conventional drugs, have developed side effects or achieved recommended cumulative dose, where comorbidities pose unusual therapeutic challenges, or may be as intermittent, rotational or combination treatment alternatives.

COVID-19 Infection: The Virus and Its Origin, the Variants, the Immune Defense, the Multiorgan Autoimmune Reactions, and the Targeted Treatments

Background: SARS-CoV-2, the virus responsible for the current COVID-19 infection pandemic, has caused substantial damage and negative impacts in the world, including physical sickness, mental illness, death, society lock down, work interruption, and productivity reduction. From the onset in early 2020, the pandemic has not yet totally subsided as of July 2022. Although great efforts have been made to understand the nature of this pandemic by the medical and scientific communities, a comprehensive review of this pandemic has not been reported. Purpose: We aimed to perform a thorough review of the subject in order to come to a better understanding of the origin of the virus, its mutations and their corresponding health effects, its pathophysiology, and its responses to therapeutic intervention. A more comprehensive set of data on these subject matters, if available, would give healthcare providers a valuable tool in formulating the best methods to respond to the current disease and prevent the disease from spreading in the future. Method: An extensive literature search on the subjects of COVID-19 was conducted regarding the possible origin of the viral pathogen, its evolutionary changes and health impacts, the world’s responses to COVID-19 and outcomes of their responses, and healthcare professional’s actions to understand and manage the disease and the results of their actions. To gather these data, websites of PubMed and Google Scholar were utilized for the search with the following keywords: Pandemic, COVID-19, coronavirus, SARS, SARS-CoV, SARS-CoV-2, origin, pathogenesis, and treatment. Results: Our review revealed data that points to an interesting autoimmune phenomenon where most seriously sick patients affected by COVID-19 were documented by an IgA-dominant immune response to the pathogen, along with a neutrophil-directed infiltration to the vital organ in the lung aveola, resulting in critical lung injury, leading to respiratory failure, multi-organ failure, and death. Surprisingly, this IgA-mediated and neutrophil-directed disease pattern is nearly identical to a group of IgA-mediated autoimmune skin diseases, such as dermatitis herpetiformis, IgA bullous dermatosis, and IgA pemphigus, which respond well to treatment by dapsone, a sulfone class of antibiotic/anti-inflammatory drug. Moreover, the usefulness of dapsone was supported by a small clinical study. In addition, systemic corticosteroid, a trusted anti-inflammatory medication, has been used in this pandemic with variable degrees of success. Conclusion: The data collected from our review of the subject, together with our prior search knowledge, compel us to conclude that the underlying pathophysiology that causes serious respiratory distress and multi-organ failure is most likely to be autoimmune in nature and that strategies to counter these multifacet autoimmune disorders would be the most valuable in life-saving. Specifically, we identified clinical and laboratory evidence pointing to IgA autoimmune reaction as a key factor that causes significant mortality in many patients. Accordingly, we proposed the utilization of a combination of dapsone, corticosteroid, and anti-thrombotic drugs in severely ill patients at the earliest point of the disease process. The autoimmune multi-organ syndrome may explain the pathogenesis of COVID-19 as well as Post-COVID conditions and may guide healthcare professionals in a better direction to manage the disease. The possible origin of the viral pathogen may shed light on a better understanding of the pathogenesis of the disease.

Managing panniculitis in alpha-1 antitrypsin deficiency: Systematic review of evidence behind treatment

AIM To systematically review literature for management of alpha-1 antitrypsin deficiency(AATD) panniculitis. METHODS Multiple databases were searched using combinations of pertinent terms. Articles were selected describing panniculitis treatment in patients with AAT < 11 μmol and/or PiZZ genotype, with no language limitation. All relevant articles were accessed in full text. Independent review of abstracts and full manuscripts was conducted by 2 reviewers, and quality assessment by one reviewer(checked by a second). Data extraction was conducted byone reviewer(checked by a second). Narrative synthesis only was conducted, as data were unsuitable for metaanalysis.RESULTS Thirty-two case reports and 4 case series were found. Augmentation therapy(infusions of plasma-derived AAT) was the most successful, with complete resolution of symptoms in all patients. Dapsone is a less expensive option, and it achieved clinical resolution in 62% of patients, but it is very poorly tolerated. Among other single-agent antibiotics, doxycycline was the most successful with complete clinical resolution seen in 33% of patients. Immunosuppressants were largely unsuccessful; 80% of patients exhibited no response. Liver transplantation and therapeutic plasma exchange displayed complete resolution in 66% of patients. Other strategies, such as non-steroidal anti-inflammatory drugs or antibiotics other than dapsone did not show sufficient response rates to recommend their use. Authors note the risk of bias imposed by the type of evidence(case reports, case series) available in this field.CONCLUSION Dapsone is the recommended first line therapy for AATD panniculitis, followed by augmentation therapy. Plasma exchange may be an alternative in the setting of rapidly progressive disease.