Dapsone Therapy Research Articles

The adverse drug effects of dapsone therapy in leprosy: a systematic review

Objectives: To establish the rate of adverse drug reactions (ADR) when dapsone is given in leprosy multi-drug therapy (MDT). This paper reviews the reporting of ADRs by systematic review of the databases Ovid Medline, Ovid Embase and Global Health according to pre-specified eligibility criteria. Results: The search identified 5859 relevant citations. These publications were divided into two data sets and reviewed for their documentation of ADRs. One hundred and fourteen publications reported ADR as the primary outcome and 98 papers reported the efficacy of treatment. Of the 114 papers included, 79 were case reports, 23 retrospective studies, 7 prospective studies and 7 literature reviews. Dapsone Hypersensitivity Syndrome (DHS) was reported most frequently as an adverse effect, then anaemia (haemolytic and not otherwise specified), cutaneous eruptions, gastrointestinal disturbance and hepatitis. Eleven studies report a mean rate of DHS as 1.22% and an average fatality rate in 8 studies of 11.24%. Of the 98 papers reporting treatment efficacy, 33 papers reported ADRs to medications other than dapsone and 36 publications had no documentation of adverse effects. Conclusion: Most publications report ADRs in case reports, many from India. DHS was the most commonly reported ADR, followed by individual features of the syndrome. Many studies lack patient information with many not reporting ADRs. Our findings show that improved prospective monitoring of adverse events associated with dapsone is needed. We propose that all patients should be tested with a full blood count before starting MDT and repeated after 4–8 weeks with mandatory follow-up. This would facilitate detecting ADRs including DHS and dapsone-associated anaemias.

27-Year-Old Woman With Fever, Headache, and Anemia

27-Year-Old Woman With Fever, Headache, and Anemia

Dapsone: An Old but Effective Therapy in Pediatric Refractory Immune Thrombocytopenia.

There are no definitive guidelines for management of chronic or refractory immune thrombocytopenia (ITP) in children. Dapsone is an inexpensive and efficacious, yet neglected, therapeutic option for treatment of chronic ITP. We evaluated the efficacy and safety of dapsone in the management of chronic ITP in children. Children with chronic ITP < 14years with minimum grade 2 bleeds refractory to either splenectomy/rituximab/eltrombopag; who were offered dapsone therapy were retrospectively analyzed. Dapsone intolerance and G6PD deficiency were excluded. Dapsone was started at a dose of 1-2mg/kg/day. Response to dapsone as per international working group definitions, time to response along with side-effects were noted. Forty-four children enrolled; 29 analyzed. Nineteen were refractory to rituximab, 8 to splenectomy and 6 to eltrombopag. Median age was 9.8years (3-14) with 16/29 males. Median dapsone dose was 1.59mg/kg/day (range 1-2.1). Overall response was seen in 21/29 (72%): Complete Response in 7/29 (24%), Partial Response in 14/29 (48%). All responses were sustained for minimum 3months. Median duration to response was 2.9months (2-6.6). Median follow up was 28months (6-73) and relapse rate-21%. Major side effects noted: Methemoglobinemia-01, skin ulceration-02. In three cases dapsone could be tapered and stopped without relapse. Dapsone is an economical and efficacious agent with good safety profile in childhood chronic/refractory ITP.

IgG/IgA-pemphigus — extremely rare blistering autoimmune diseases

Purpose. To present a clinical case of IgG/IgA pemphigus in a 32-year-old woman.&#x0D; Material and methods. Clinical and laboratory examinations were performed to diagnose the disease: cytological examination of an impression smear from the bottom of the erosion, histological examination of a skin biopsy sample from the lesion, immunofluorescent examination of a biopsy sample of visually accessible unaffected skin.&#x0D; Results. Clinical manifestations of the disease were similar to Duhring's dermatitis herpetiformis, morphological ones to pemphigus vulgaris, but immunofluorescent examination of the skin biopsy sample in equal measure revealed deposits of both IgG and IgA in the epidermis, which allowed to determine a diagnosis of IgG/IgA pemphigus. Dapsone therapy at a dose of 100 mg per day led to a significant improvement in the patient's condition.&#x0D; Conclusion. Diagnosis of bullous dermatoses requires immunofluorescent examination of a biopsy sample of visually accessible unaffected skin. Dapsone was an effective medication for the patient with IgG/IgA pemphigus.

An unusual presentation of De-novo Histoid leprosy clinically mimicking as neurofibromatosis

Histoid leprosy is a rare and uncommon variant of lepromatous leprosy which generally occurs following resistance to dapsone therapy or relapse after dapsonemonotherapy or multidrug therapy. Rarely, it can occur de novo without any history of treatment. We present one such rare case of histoid leprosy mimicking neurofibromatosis presented in a 43 year old male.

Hematological alterations in lepromatous leprosy: A cross-sectional observational study

BackgroundDapsone has been the mainstay for the treatment of leprosy since its discovery in the 1940s. However, hematological disturbances are not uncommon in leprosy patients on daily dapsone therapy. Hence, the present study was conducted to document the hematologic alterations observed in lepromatous leprosy patients treated with Dapsone 100 mg daily. MethodologyA cross-sectional observational study was conducted amongst 32 lepromatous leprosy patients treated with Dapsone 100 mg daily. A complete hemogram was conducted for all the study recruits. The test results were compared against the standard average values for adults for the given variables. The one sample t-test was employed to compare the difference between the study values and the standard normal values for adults. The statistical significance was considered at p < 0.05. ResultsThe study reveals a marked decrease in hemoglobin concentration in patients on dapsone, 100 mg daily. Other hematological alterations found were reduced platelet count, reduced mean platelet volume, reduced Hematocrit, reduced Mean Corpuscular hemoglobin, reduced Mean Corpuscular hemoglobin concentration. (p < 0.05). ConclusionTreatment of lepromatous leprosy with 100 mg daily Dapsone therapy may lead to hematological alterations. These findings are suggestive of dapsone-induced hemolysis.

Dapson Tedavisine Bağlı Hemoliz Görülen Bir Hastada Hemoglobin D Saptanması

Dear Editor,Several mutations occur in the genes that encode globin chains which are a part of hemoglobin (Hb) structure. Such mutations give rise to formation of different hemoglobin variants.1 One of these hemoglobin variants (Hb C, D, E, F and S) is Hb D [β 121 Glu→Gln (GAA→CAA)]. Hb D occurs in 0.2% in Turkey.2 Molecular analysis has revealed many types of Hb D. Hb D-Los Angeles or Hb D-Punjab is the most common type.3 Clinically, heterozygous types of Hb D do not produce any hematological manifestations. However, mild-to-moderate cases of hemolysis have been rarely reported in conjunction with its homozygous forms.4 In this study, we present a case of hemolysis due to dapsone theraphy in coexistence with Hb D. A 17-year-old female patient who had been on colchicin treatment for Behçet’s disease for the last 3 years presented to the rheumatology department with persistent painful sores in her mouth. Following assessment of the patient, treatment with dapsone 50 mg tablets, three times daily was started by the rheumatology department. Two months after initiation of medical treatment, the patient presented to the hematology department with complaints of pallor, chills and fatigue. Her diagnostic work-up showed the following: Hb: 11.2 g/dL (11.9-14.6), MCV: 92.8 fL (81.8-95.5), PLT: 307 x 10³/uL (173-390), reticulocyte count: 264.5 x 103/uL (17-63.8), reticulocyte%: 7.09%, LDH: 367 U/L (0-279), total bilirubin: 2.7 mg/dL (0.1-1.5), indirect bilirubin: 1.5 mg/dL (0.08-1.1) and haptoglobulin&amp;lt; 30 mg/dL (30-200). Peripheral smear showed the presence of spherocytes and fragmented red blood cells. Direct and indirect Coombs tests were negative. Papain antibody and glucose 6 phosphate dehydrogenase (G6PD) tests were negative. Her laboratory values before dapsone therapy were as follows: Hb: 14.2 g/dL, MCV: 85.2 fL, PLT: 309 x 10³/uL. Initially, hemolytic anemia induced by dapsone was considered as possible diagnosis and dapsone treatment was discontinued. Laboratory work-up after three weeks showed a reticulocyte count of 125.6 x 10³/uL, % reticulocyte of 3.49%. These results prompted a request for hemoglobin electrophoresis based on a preliminary diagnosis of thalassemia. Hb D was found as 41.65% (Figure 1). Moleculer genetic test (DNA analysis) was found to be Hb D-Los Angeles [c.3646&amp;gt;C(p.E122Q)(p.Glu.122Gln)(Heterozygous)]. Hemoglobin electrophoresis was performed from the blood sample of her father and revealed Hb D of 88.13% and HbA2 of 3.91%. Her father was diagnosed with beta-thalassemia minor and Hb D. Drugs are a rare cause of hemolytic anemia. Dapsone is known to cause oxidative hemolysis. This situation has been reported to result from the direct toxic effect of a hydroxlamine derivative formed by N-hydroxylation to erythrocytes.5 Hemoglobin electrophoresis was performed for the patient during follow-up due to persistent hemolysis and a rare Hb variant was detected. This was a surprising finding for us, the physicians who were following the patient because her previous hemogram and biochemical analyses were not suggestive of thalassemia. Thus, we were facing two rare conditions at the same time: drug-induced hemolysis and Hb D.As a result; coexistence of hemolysis due to dapsone and Hb D is a rare condition. Since Hb D was found to be heterozygous in the patient, we think that this condition did not have clinical effect on hemolysis. To the best of our knowledge, this is the first case in which Hb D is detected in a patient with hemolysis due to dapsone.

DRESS syndrome: A life-threatening complication of dapsone therapy

DRESS syndrome: A life-threatening complication of dapsone therapy

Study on estimation of glucose-6-phosphate dehydrogenase in patients prior to initiation of dapsone therapy in leprosy

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Administration of dapsone in glucose-6-phosphate dehydrogenase (G6PD) deficient patients can lead to hemolysis which may be severe enough to warrant discontinuation of the drug. Screening for G6PD deficiency in leprosy patients before initiating treatment can prevent such adverse events.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; Medical records of all leprosy patients presenting between 1st January 2018 to 30th June 2018 were reviewed. G6PD levels, if done, were recorded for all patients needing dapsone therapy.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Of the 62 patients requiring treatment with dapsone (43 outpatients and 19 inpatients), G6PD estimation was done in 43 cases, i.e., 60.46% (26/43) of outpatients and 89.4% (17/19) of inpatients.10 patients were found deficient (6/26 outpatients and 4/17 inpatients).&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; G6PD levels were not uniformly estimated in all patients requiring dapsone therapy. It was done more commonly estimated in inpatients (89.4%) when compared to outpatients (60.46%). The deficient G6PD levels were seen in 16% cases.&lt;/p&gt;

Dapsone hypersensitivity syndrome overlaps reversal reaction in leprosy patient

Background: Leprosy is a chronic granulomatous infectious disease that primarily involves the skin and peripheral nerve and is caused by Mycobacterium leprae . Clinical features may vary depending on the patient’s immune response. Reversal reaction due to increased immunity is common after treatment in patients with borderline leprosy. Dapsone hypersensitivity syndrome (DHS) is an adverse effect from dapsone therapy that may occur in 5-6 weeks to 6 months after initial treatment. Case Illustration: A 47-year-old female complained of a spreading red patches on the skin of her trunk and extremities for three weeks duration. She also felt itchiness and tight sensation of rash. She experienced fever, pain, and numb lesions. She was diagnosed with leprosy and already had her sixth Multi Drug Therapy-Multi Bacillary (MDT-MB) regimen. From physical examination, on thoracic, abdominal, and extremities regions, multiple erythematous macules with hypoesthesia, sharply marginated ranging from size 3 to 5 cm along with discrete erythematous papules were found. Bacteriology index was zero. Patient was diagnosed with borderline leprosy with reversal reaction. After treated with prednisone, the patches became better, but the rash was still progressive. The rash had gotten significantly better after dapsone therapy was discontinued. Discussion: Borderline leprosy is immunologically unstable and can be complicated by reversal reactions. Reversal reaction is due to increased immunity and usually occurs after MDT treatment. Conclusion: Reversal reaction got better with prednisone, while DHS was significantly improved after stopping dapsone therapy. D rug patch test should be conducted after the lesion resolves i n order to establish DHS. Keywords : dapsone hypersensitivity syndrome, leprosy, reversal reaction

MON-LB025 An Artificially Low HbA1c as a Result of Dapsone Therapy

Since the 1970s, hemoglobin A1c (HbA1c) has been incorporated in clinical practice to monitor glycemic control. Furthermore, in 2010, the American Diabetes Association included HbA1c as a diagnostic criterion for diabetes. According to Zion Market Research, the global HbA1c market is expected to reach 2.2 billion USD by 2021. HbA1c is useful to clinicians because it provides a broader perspective of a patient’s glycemic control compared to the snapshot granted by blood glucose measurement. The erythrocyte membrane is permeable to glucose, allowing the sugar to react nonenzymatically with the N-terminal amino group of the beta chain via a ketoamine linkage. This process occurs continuously over the erythrocyte lifetime, which results in HbA1c representing a three-month window which reflects patients’ glycemic control. However, instances exist in which the utility of HbA1c diminishes in diabetic monitoring. We present the 8th case report in which dapsone interfered with the ability of HbA1c to accurately depict the glycemic status of a patient. The patient is a Caucasian male who was started on dapsone therapy on December 9th, 2013 for lichen planus. HbA1c values ranged from 7.2-8.9% during the four years before initiation of dapsone therapy. Two months after dapsone was started, HbA1c dropped to 6.9% and subsequently remained at 4.8%-5.8% until the drug was discontinued on May 11th, 2016. Three months later, HbA1c levels increased to 7.6% and ranged from 7.3%-7.8% until June the following year. In addition, fingerstick glucose values during this period also suggested poor glycemic control. Because HbA1c levels decreased in the presence of elevated fingerstick glucose, fructosamine levels were analyzed. Fructosamine refers to proteins that are nonenzymatically glycated via ketoamine linkages at the N-amino terminal (Danese et al 2015). Because albumin is the major serum protein, fructosamine primarily reflects glycated albumin. As opposed to erythrocytes, albumin exists in the blood for about two weeks. Therefore, fructosamine, indicates recent glycemic status for a narrower window than HbA1c. On July 23rd, 2015 the patient’s fructosamine levels were 299 mcmol/L (reference range: 200-285 mcmol/L) while HbA1c was 4.9%. As a result, the fructosamine results suggest that the patient’s glycemic control had not improved as suggested by the HbA1c values. A side effect of dapsone is hemolytic anemia. During the time that the patient was on dapsone, his hemoglobin levels dropped from about 14 g/dL to 11.7 g/dL. Simultaneously, total bilirubin levels increased from approximately 0.5 mg/dL to 0.9 mg/dL, suggesting a hemolytic anemia. We propose that dapsone generated a hemolytic anemia in this patient, which caused his HbA1c values to be unreliable in monitoring his glycemic control. Clinicians should be wary when monitoring the course of diabetic disease in patients on dapsone therapy. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Abstract #250 An Artifically Decreased Hba1C Due to Dapsone Therapy

Abstract #250 An Artifically Decreased Hba1C Due to Dapsone Therapy

A new Mycobacterium leprae dihydropteroate synthase variant (V39I) from Papua, Indonesia

Indonesia had the third highest number of new leprosy cases worldwide in 2017. This disease is still prevalent in Papua province, where the number of new cases in 2014 (3.0 cases per 10,000 people) is considered highly endemic and is well above the World Health Organization's (WHO) cutoff of <1 new case per 10,000 people. Since 1995, the WHO has supplied Papua province with a multi-drug therapy (MDT) in which multibacillary (MB) patients are treated with rifampicin, clofazimine, and dapsone and paucibacillary (PB) patients are treated with rifampicin and dapsone. Recent published data on global drug resistance reported cases of dapsone resistance in relapsed and newly diagnosed cases in Indonesia during this period. The detection of specific point mutations in folP1 that encode dihydropteroate synthases (DHPS) is used exclusively to identify dapsone resistant strains of Mycobacterium leprae. The purpose of this study was to test for the presence of folP1 mutations in M. leprae strains isolated from patients residing in Papua Island, Indonesia who responded less effectively to dapsone. This study identified a folP1 point mutation that changed a valine (V) residue at amino acid position 39 (from the N-terminus) to isoleucine (I) (V39I) of DHPS. The V39I variant is located within an α-helix motif that may not much affect its structure. Molecular docking analysis indicated that the binding affinity of the V39I variant was slightly reduced as compared to the wildtype of DHPS. The decreasing of affinity may have a consequence of increasing inhibition constants (Ki) of dapsone on the variant V39I of DHPS. The data suggest that the DHPS V39I variant might cause less sensitive to dapsone. However, in vivo studies (e.g., mouse footpad model) are needed to confirm the effect of this DHPS variant on dapsone therapy.

Neutropenia, Hypoxia, and the Complexities of Emergency Medicine: A Case of Dapsone-Induced Methemoglobinemia

Methemoglobinemia is a rare dyshemoglobinemia that can be difficult to diagnose due to its nonspecific symptomatology and infrequent occurrence. A number of commonly used medications have been known to contribute to this disease process that results in acute hypoxemia. A 60-year-old man with history of acquired immunodeficiency syndrome presented to the Emergency Department (ED) with asymptomatic hypoxia. Supplemental oxygen proves to be ineffective in treating his low oxygen saturation. Numerous testing modalities are performed in the ED focused on an infectious versus pulmonary etiology prior to coming to the conclusion that the source is methemoglobinemia induced by dapsone therapy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This article discusses the basic pathophysiology of the disease and the expected clinical findings. Patient outcome is correlated with prompt identification and discontinuation of the offending agents leading to the excessive accumulation of methemoglobin in the circulatory system. This makes it crucial that emergency providers know the symptomatology of the disease to facilitate appropriate treatment therapy.

Rhinosporidiosis of maxillary sinus: A case report

Rhinosporidiosis is a chronic granulomatous inflammatory disease inducing polyps of the affected mucous membrane and is caused by Rhinosporidium seeberi. Seldom mimicking other more malignant and vigorous pathologies of the involved part. As rhinosporidiosis primarily affects orofacial and sino-nasal region, it is of great value to the oral physician, oral radiologist and oral surgeon and a necessary differential diagnosis to be kept in mind for sino-nasal masses. As the causative organism is an aquatic protistan parasite and cannot be cultured in vitro, the diagnosis depends on clinical and histopathological findings. Treatment is complete surgical excision but recurrence is quite common at 10% to 30%. Use of cryosurgery and electrocautery reduce the recurrence. Also, systemic dapsone therapy is used as an adjunct to surgical intervention and helps in preventing recurrences. In this case report, the clinical, radiological and pathological features of a case presenting in a 55-year old male has been described. The involvement, erosion and destruction of the various walls of maxillary sinus and maxillary osteomyelitis as in this case is very rare and only a few cases have been recorded in the literature. The surgical and pharmacologic management along with 18 months follow up has been discussed and a short review of literature has been made.

A Retrospective Analysis of 122 Immune Thrombocytopenia Patients Treated with Dapsone: Efficacy, Safety and Factors Associated with Treatment Response

Dapsone has been used in the treatment of patients with immune thrombocytopenia (ITP) since the late 1980s. It is a drug that is inexpensive and well tolerated, but unfortunately, it is underused worldwide due to the lack of information regarding its mechanism of action, efficacy rates and safety profile. Our institution has an extensive experience with the drug, for it has been used as the standard 2nd line therapy in our ITP patients for the last 20 years.In this study we aimed to assess the efficacy rate, frequency and gravity of side effects of dapsone therapy in ITP patients. As a secondary endpoint, we wanted to evaluate the possible clinical factors associated with a treatment response.This was a single-center retrospective study, where medical charts of ITP patients in follow-up at our outpatient clinic in the period of 2011 to 2017 were reviewed for identification of patients treated with dapsone. Inclusion criteria were diagnosis of ITP and dapsone treatment for a period of at least 15 days. The recommendations from the international working group were used for the definitions of ITP diagnosis, classification and assessment of treatment responses (Rodeghiero F et al, 2009).Medical charts from 272 ITP patients were reviewed, with the identification of 147 patients treated with dapsone during the follow-up period. Eight patients did not meet inclusion criteria due to short duration of dapsone treatment. Seventeen patients were excluded from the study, due to: concomitant use of other therapies for ITP (n=8), important missing data (n=7) and significant hypersplenism (n=2). The final total of evaluated patients was 122. Baseline characteristics of these patients are shown in Table 1. Dapsone treatment was normally initiated at the dose of 100mg/d. Only 22% of patients were screened for G6PD deficiency before dapsone initiation. Median treatment duration was 6 months, with a maximum treatment duration of 15 years. The median study follow-up period was of 3.4 years (1.3 months-17.6 years).The overall response rate in this cohort was 66%, including 24% of complete responses. Clinical characteristics associated with a greater chance of treatment failure were previous splenectomy (p=0.003) and three or more previous therapies (p=0.02). Among all responders, in 24% a relapse occurred while on dapsone treatment. Therefore, a sustained response was observed in 51% of the study cohort. Patients with a complete response had a much lower relapse rate, of only 7%. Interestingly, 81% of the responders maintained the response after the interruption of treatment, for a median time of 26 months. As expected, splenectomy was performed later on in only 16% of the responders, a much lower rate than observed in non-responders (61%).Side effects were reported in 16% of the patients in this cohort: symptomatic hemolytic anemia (n=5), symptomatic methemoglobinemia (n=5), gastrointestinal symptoms (n=4), and others (n=5). Treatment was interrupted due to side effects in 11% of patients, the main cause in these cases was hemolytic anemia (n=5), followed by methemoglobinemia (n=4). Elevations of methemoglobin levels were observed in 83% of the evaluated patients (n=45), but these elevations were usually mild, with a median methemoglobin level of 2,6%. Methemoglobinemia occurred more often in older patients. Reductions in hemoglobin (Hb) levels during the use of dapsone were seen in 94% of the patients. Median Hb fall was 1,7g/dL. Only 49% of the patients reached Hb levels consistent with a diagnosis of anemia. Responders presented significantly greater reductions in their Hb levels than non-responders: median Hb drop of 1.9g/dL vs 1.2g/dL (p=0.004) (Figure 1).Our findings suggest that dapsone has adequate efficacy and is well tolerated in ITP patients. We observed a sustained response in 51% of the patients, that lasted for over 2 years after the suspension of the drug in most of the responders. When used as a 2nd line therapy, it has a role as a splenectomy-sparing agent. The main side effects observed were hemolysis and methemoglobinemia, but in general they were mild and well tolerated. Patients with previous splenectomy and greater number of treatments were less likely to respond to dapsone. Although the mechanism of action is still unclear, our observation that the degree in the drop of Hb is greater in responders suggests a possible role of the blockage of the reticuloendothelial system in the therapeutic effect of the drug. DisclosuresDe Paula:Hematology and Transfusion Medicine Center, University of Campinas: Employment.

Linear IgA Disease and Celiac Disease: Are They Mutually Exclusive?

Adult Linear IgA disease or linear IgA bullous dermatoses(LABD) is a idiopathic or drug-induced autoimmune blistering disease characterized by the linear deposition of IgA at the dermoepidermal junction. Only 0.5 to 2.3 cases of Linear IgA are estimated to be reported each year. Although the clinical features of this disorder can be difficult to distinguish from dermatitis herpetiformis, the distinct immunopathologic findings in LABD and the absence of an associated gluten-sensitive enteropathy has historically confirmed the status of LABD as a distinct disease. We present a case of a patient with LABD with a concomitant high-gluten sensitivity. A 42 year-old women with a history of recurrent gastric ulcers presented with skin blisters. The patient stated she also has noticed that she is very sensitive to wheat containing products including cleaning supplies and shampoos. Upon examination, a clinical diagnosis of dermatitis herpetiformis was made. An upper endoscopy was performed which was positive for gastric ulcers. On duodenal biopsies, histology showed increased intraepithelial lymphocytes with villous blunting. On biochemical testing the patient was found to have an iron deficient anemia with no elevated levels of IgA in her serum. Transglutaminase Antibody IgA Titers were > 250.0, gliadin deamidated Ab, IgG and IgA were both elevated. A skin biopsy was performed which showed linear deposits of IgA seen at the dermo-epidermal junction. Treatment was initiated with dapsone therapy in which the patient was responsive over the course of treatment. This case illustrates a rare condition of LABD in a patient with concomitant celiac disease. This shows the importance of recognizing that a patient can present with linear IgA disease and continue to display strong gluten sensitivity. A high index of suspicion must be mainitained in patients with presumed celiac disease and dermatological manifestations who are not responding adequately to gluten free therapy.

Dapsone safety in hematology patients: Pathways to optimizing Pneumocystis jirovecii pneumonia prophylaxis in hematology malignancy and transplant recipients.

Dapsone may be used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis in hematology patients receiving immunosuppressive therapy or after hematopoietic stem cell transplant (HSCT) in the setting of trimethoprim-sulfamethoxazole (TMP-SMX) adverse drug reaction (ADR) history. Dapsone-induced hematological toxicities such as oxidative hemolysis may limit use in these patients and modern assessments of dapsone allergy cross-reactivity in non-HIV patients with a sulfonamide allergy are largely absent. The aim of this single-centre, retrospective study was to describe dapsone usage in hematology patients requiring PJP prophylaxis, including HSCT recipients, over a 12-month period in terms of indications, incidence of dapsone-attributed oxidative hemolysis, and immune cross-reactivity in those previously labeled with a sulfonamide allergy, as well as describing potential opportunities for first-line TMP-SMX PJP prophylaxis reintroduction. Of 24 patients meeting the study inclusion criteria, 12 (50%) were receiving dapsone PJP prophylaxis post-HSCT. No cases of breakthrough PJP infection were noted. Sixteen patients (67%) were initiated on dapsone to avoid the perceived risk of further myelosuppression with TMP-SMX and five patients (21%) because of prior delayed immune-mediated allergy to TMP-SMX. None experienced rash with dapsone therapy. Six patients (25%) were successfully rechallenged on TMP-SMX, including one patient with prior TMP-SMX-associated rash. Four (17%) patients had confirmed oxidative hemolysis, all resulting in dapsone cessation. Dapsone PJP prophylaxis in hematology patients was effective and safe, with nonlife threatening dapsone-related hemolysis noted in a small number. An absence of sulfonamide allergy cross-reactivity was noted, suggesting greater TMP-SMX rechallenges or desensitization could be considered in those receiving dapsone.

Falsely Decreased HbA1c in Diabetic Patient due to Dapsone

HbA1c and fructosamine are glycated proteins used to monitor glucose control over time in patients with diabetes. Many factors can affect HbA1c values leading to spuriously low or elevated results. We report a case of a 67 year old woman with type 1 diabetes with good glycaemic control based on HbA1c values ranging from 44-52 mmol/mol over 7 year follow-up. She was commenced on dapsone for treatment of granuloma anulare; four months into this treatment her HbA1c was 25 mmol/mol. The record of self-monitoring blood glucose showed that most of her glucose values were within the recommended target. She had normal hypoglycaemia awareness and reported only 3 episodes of symptomatic hypoglycaemia in the preceding four months. Given the history of dapsone therapy and the discordant result of self-monitoring blood glucose and HbA1c concentrations, we suspected methemoglobinemia as a cause. Dapsone treatment has been recognised to cause falsely low HbA1c results by two mechanisms: haemolysis by reducing the erythrocyte life span and the formation of methemoglobin which interferes with HPLC used to measure HbA1c. In conclusion, dapsone is commonly used in diabetic patients who have other autoimmune diseases. HbA1c monitoring in patients treated with dapsone is unreliable and other markers such as capillary blood glucose records, and other glycated proteins such as fructosamine should be used as an alternative for monitoring of glucose control is such patients. Table 1 Laboratory resultPrior to dapsone4 months after dapsoneHb level (g/dl)13.211.7MCV (fl/cell)92105Absolute reticulocyte counts (109/L)53303Total bilirubin level (micromol/L)1312Methehaemoglobin fraction(%)4.7HbA1c (mmol/mol)X25 Disclosure K. Aljenaee: None. S. Haji Ali: None. A. Pazderska: None.

Tuberculosis and Leprosy Coinfection: A Perspective on Diagnosis and Treatment

Both leprosy and tuberculosis (TB) are known to have similar geographic endemicity. In the setting of coinfection, interferon-gamma release assays (IGRAs) to detect latent TB can be falsely positive. We report a case of leprosy with a positive IGRA and asymptomatic active pulmonary TB. Minocycline and dapsone therapy was initiated during the workup for TB and changed to rifampin (Rif), isoniazid, pyrazinamide, and ethambutol, with the addition of dapsone once coinfection was confirmed. Our review of the literature revealed a preponderance of coinfection reported with borderline and lepromatous disease. Ten patients were diagnosed with leprosy as the first infection; 7 of these patients (70%) were treated with Rif before TB diagnosis, and 70% (7/10) of coinfected patients were on steroids. If treatment for leprosy is a consideration before ruling out active TB, then minocycline may temporarily replace the Rif. The dire implications of Rif monotherapy in undiagnosed coinfection may warrant chest radiography with or without sputum microbiology as routine initial workup for all leprosy cases.