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Dapsone renal failure
Metrics details. However, the use of dapsone may be associated with a plethora of adverse effects, some of which may involve the pulmonary parenchyma.
DHS typically presents with a triad of fever, skin eruption, and internal organ lung, liver, neurological and other systems involvement, occurring several weeks to as late as 6 months after the initial administration of the drug.
DHS must be promptly identified, as untreated, the disorder could be fatal. Eosinophilic infiltrates, pneumonitis, pleural effusions and interstitial lung disease may be seen. This syndrome is best approached with the immediate discontinuation of the offending drug and prompt administration of oral or intravenous glucocorticoids. An immunological-inflammatory basis of the syndrome can be envisaged, based on the pathological picture and excellent response to antiinflammatory therapy.
Since dapsone is used for various indications, physicians from all specialties may encounter DHS and need to familiarize themselves with the salient features about the syndrome and its management. Dapsone has been used for many indications because of its antibiotic and anti-inflammatory effects [ 1 ]. Not only has it been the drug of choice for the treatment of leprosy Hansen's disease since the middle of the 20 th century, but it has also been used for the treatment of brown recluse spider bite [ 12 ], dermatitis herpetiformis, vesicobullous dermatoses, cutaneous vasculitis, polyarteritis nodosa, nodulocystic acne, cutaneous mycetoma and multiples other dermatologic indications all of which may be seen as manifestations in certain occupational diseases [ 1 ].
This has led to increasing incidence of dapsone-related complications. Hemolysis more likely to occur with deficiency of glucose 6-phosphate dehydrogenase or G6-PDbone marrow aplasia, renal disease, peripheral neuropathy, methemoglobinemia, nausea, dizziness, fatigue and other systemic manifestations may occur singly or in combination in patients on dapsone therapy. Of these, DHS is characterized by the onset of fever, skin eruption and internal organ involvement several weeks to as late as 6 months after patients are given this drug.
Untreated the syndrome can lead to severe organ dysfunction and even death. The definitive mechanism for DHS is unclear, but it is hypothesized that it is mediated by immune activation and elaboration of inflammatory cytokines.
This case report emphasizes the pulmonary effects associated with DHS. The following sections provide an overview of the presentations, pathogenesis, diagnosis and management of DHS. A twenty-one-year old previously healthy nursing student, with no significant past medical or surgical history, presented with an apparent reaction to an insect bite on her left shin. She was evaluated and based on the presumed diagnosis that this represented a hypersensitivity reaction to an insect bite, and she was treated with dapsone mg twice a day for 7 days as an anti-inflammatory agent.
This was based on some data supporting the use of this drug for insect bites [ 2 ], although this now appears to be a controversial approach. After seven days of therapy, the patient developed progression of her symptoms, developing fever with chills, myalgia and nausea associated with diffuse abdominal pain, dark-colored urine and jaundice. She also noticed a new onset non-pruritic, ascending, maculo-papular skin eruption, with progressive shortness of breath.
She denied cough, hemoptysis, or chest pain at this time. Oral mucosa was normal, with no visible lesions. Neck examination was supple, with no palpable lymphadenopathy or evidence of thyroid enlargement. Lung examination revealed bilateral diffuse crackles, decreased breath sounds in both bases and dullness to percussion. Cardiac examination showed tachycardia without audible murmur while the abdominal examination revealed hypoactive bowel sounds with diffuse mild tenderness on deep palpation, without palpable organomegaly or evidence of rebound tenderness.
The patient demonstrated a diffuse maculopapular eruption with sparing of the hands, feet, and mucosa. There was no blanching on pressure.
There was a healing ulcer on her left shin with a dried-up scar site of presumed insect bitewithout surrounding erythema or other signs of inflammation or infection. The absence of significant necrosis or surrounding inflammation suggested that the symptoms the patient was experiencing were independent of the insect bite.
The admitting laboratory data is provided in Table 2. Liver function abnormalities consistent with transaminitis were seen. The peripheral smear review showed a normocytic, normochromic anemia with mild neutrophilia and toxic granulations. The patient also demonstrated mild anisocytosis, poikilocytosis and reticulocytosis. The urine sample tested positive for blood but the patient had negative urine, blood and stool cultures.
A chest roentgenogram was done on admission and showed a diffuse bilateral air space disease involving the majority of the lung with sparing of the lung apices with bilateral pleural effusions. Computed tomography of the abdomen and pelvis with contrast showed gallbladder wall-thickening and mild dilatation, with small amount of abdominal fluid ascites.
Computed tomography of the chest showed bilateral infiltrates mainly on the left, along with bilateral pleural effusion Figure 1. Computed chest tomography of the patient described in this report, showing bilateral interstitial infiltrates yellow arrow and pleural effusions red arrow. Image taken at a mid-thoracic level. Based on the clinical picture of multisystem involvement, lack of a defining microbiological cause and the progression of disease, a diagnosis of DHS was made.
The patient was immediately initiated on intravenous glucocorticoids methylprednisolone with dramatic improvement in her symptoms and clinical disease. This improvement is shown in Table 2 and includes dramatic reversal of anemia, improvement in transaminitis and in inflammatory parameters. This was also evidenced by stabilization of hypoxemia with less need for oxygen supplement. DHS is characterized by a hypersensitivity response to the drug, dapsone which is a sulfone.
Dapsone 4,4'-Diaminodiphenylsulphone is used mainly as an anti-inflammatory and anti-bacterial agent for the treatment of skin diseases, bacteria, and fungi [ 1 ]. The anti-inflammatory effects of dapsone are mainly related to its interference with neutrophil chemotactic migration and adherence [ 1 ]. Other multiple mechanisms are listed in the literature. These describe suppression of neutrophil recruitment, inhibition of local production of toxic respiratory and secretory products, as well as formation of oxidants.
These not only kill bacteria but also damage bystander tissues. In addition, dapsone can inhibit the release of prostaglandins and leukotrienes by blocking their inflammatory effects [ 13 — 5 ].
A list of adverse effects of dapsone some predictable, some idiosyncratic or allergic is provided in Table 1. A rare syndrome, DHS which was first described by Allday, Loweand Barnes [ 45 ] as a hypersensitivity vasculitis syndrome [ 13 — 8 ].
The incidence of DHS ranges from 0. This variability of the latency time was explained by several factors. Some of those were related not only to the variability of the acetylators but also to the dose and the modality of treatment [ 1468 ]. This wide variability of the latency period suggests a multi-organ hypersensitivity reaction, but the exact mechanisms are unclear and reviewed later [ 4 — 7 ].
The classic triad of DHS consists of fever, eruption, and internal organ involvement Table 3. Fever, hepatitis, exfoliative dermatitis, adenopathy and hemolytic anemia might be seen in varying combinations and sequences [ 9 ]. While traditionally a hepatitis or transaminitis is seen, cholangitis has also been described as a component of the DHS [ 9 ]. Studies have shown that this syndrome may begin as early as 7—10 days after administration of the drug or as late as 6 months into therapy with dapsone.
Cutaneous lesions can range from erythematous papules as in our patient, to plaques, pustules, and eczematous lesions [ 13 — 8 ]. The severity of the cutaneous changes does not correlate with the severity or extent of internal organ involvement which may remain asymptomatic of even life-threatening [ 10 ]. Cutaneous lesions usually begin to resolve 2 weeks after stopping therapy. Some patients may also develop severe dermatitis and complications, such as the Steven Johnson Syndrome or toxic epidermal necrolysis Table 1.
These patients may experience prolonged morbidity and even mortality with the complications. Especially in severe cases, malnutrition, protein loss and secondary infection may complicate the illness, and these patients need to be monitored for complications more aggressively. In traditional DHSantibiotics have little or no role unless obvious infection, cellulitis or sepsis is present.
Infiltrative lung disease is the most common pattern of drug-induced injury [ 10 ]. This pattern can cause interstitial lung damage, alveolar damage or vasculitic involvement e. As listed in Table 3DHS can also involve the lung, with 10 cases reported in the literature. In the patient described by us, pulmonary infiltrates and pleural effusions with severe hypoxemia were present suggesting interference with alveolocapillary oxygen transfer.
Other manifestations have also been described in the literature. Table 4 summarizes the different pulmonary manifestations of dapsone. Pulmonary manifestations of the DHS are sometimes dominant features, as occurred in our patient. Manifestations have included the development of eosinophilic pneumonia [ 11 — 15 ], hypersensitivity pneumonia [ 16 ], pleural effusion [ 17 ].
Many reported cases of eosinophilic pneumonia have an associated systemic blood eosinophilia, which however, was not present in our case.
The rapid clinical deterioration seen with DHS can lead to respiratory failure as seen in our patient and sometimes death, if untreated or unrecognized. Other manifestations of this syndrome include hepato-biliary dysfunction such as jaundice[ 1 ], hepatomegaly [ 1 ]and cholangitis [ 9 ], splenomegaly[ 1 ], eosinophilia[ 113 ], photosensitivity[ 1 ], elevated sedimentation rate [ 1 ], and a mononucleosis picture that can mimic EBV and CMV infection [ 17 ].
In addition, DHS can include peripheral neuropathy [ 18 ], psychosis [ 19 ], renal involvement such as nephrotic syndrome [ 1 ] and renal papillary necrosis [ 20 ] and pancreatitis [ 17 ] as found in our patient. As listed in Table 3a maculopapular eruption, bullous disease, photosensitivity and oral erosions can occur.
The differential diagnosis of multisystem illness presenting in a patient on dapsone is shown in Table 5. These include diseases such as: DRESS syndrome and its variants, vasculitis Churg Strauss syndromeHypereosinophilic syndrome, TENS Toxic epidermal necrolysis syndromeSteven Johnson Syndrome, Still's disease, Hematological disorders leukemia, lymphomaparaneoplastic disorders and certain connective tissue disorders.
We will discuss a few of these important conditions in this section. In the case of the latter, drug rash, eosinophilia and systemic symptoms are often present. DRESS syndrome can be seen with a variety of medications, including anticonvulsants, sulfonamides, allopurinol, calcium channel blockers, NSAIDS Non-steroidal anti-inflammatory drugs and dapsone [ 21 ]. Fever, skin eruption, adenopathy, eosinophilia and internal organ involvement might also be seen [ 21 ].
It is important to note, that both disorders may overlap. A prodromal phase, similar to a flu-like illness, lasting up to14 days, may precede the skin eruption. The acute phase of TENS consists of persistent fevers, generalized epidermal sloughing and mucous membrane involvement [ 22 ]. Cutaneous vasculitis which can be part of a systemic disease needs also to be excluded. The evaluation of such patients needs a complete work-up for the presence of systemic disease.
Skin biopsy and immunofluorescence studies may also helpful in the diagnosis of cutaneous vasculitis in which immunoglobulin and complement deposition are found [ 23 ].
If dermatitis and pulmonary disease is the dominant feature, necrotizing vasculitides and Churg Strauss syndrome needs to be excluded. If dermatological manifestations dominate the presentation, with or without mucosal involvement, Steven Johnson Syndrome and TENS need to be excluded. In some patients with a dominant eosinophilia and pulmonary infiltration, PIE syndrome [ 10 ] needs to be excluded.
Laboratory tests can include a complete blood count and differential, comprehensive chemistry profile, sedimentation rate, urine analysis, arterial blood gases and a chest roentgenogram. Skin biopsy may not be specific but will assist in excluding vasculitis or hematological malignancies.
❿Dapsone syndrome with acute renal failure during leprosy treatment: case report.American Society of Nephrology | Kidney Week - Abstract Details ()
Click an icon below to load this item into your calendar. Time zone help. Erythema elevatum diutinum EDD is a rare cutaneous small vessel vasculitis with dapsone being the drug of choice.
Patient was on dapsone in the past for over 10 years, however in the last 6months was not taking any medications. Vancomycin, zosyn and dapsone mg BID were started on admission. By day 3 only dapsone was continued as imaging was without evidence of deep infection. In addition, a thin layer may be applied topically to other acne affected areas once daily.
Reassess appropriateness of dapsone therapy if no improvement after 12 weeks. Consider prophylaxis for infants born to HIV-infected mothers beginning at 4 to 6 weeks. Discontinue prophylaxis in infants with indeterminate HIV infection status when they are determined to be definitively ore presumptively HIV-uninfected.
Do not discontinue prophylaxis in HIV-infected infants younger than 12 months. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs.
Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.
Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease. Duration of prophylaxis for ALL is from induction to the end of maintenance. Recommended for patients receiving alemtuzumab or corticosteroids at doses equivalent to more than 0.
Prophylaxis is recommended for patients with AML and solid tumors for the duration of chemotherapy. HIV-infected infants and infants whose infection status remains unknown should continue to receive prophylaxis for the first year of life.
A dose of mg PO once daily, increasing the dose by 50 mg every 1 to 2 weeks until remission occurs has been used. Subsequently, reduce dosage to lowest effective maintenance dose. Maximum oral dosage information not established; safety and efficacy of topical gel not established. Dapsone can cause toxic hepatitis and cholestatic jaundice, however, specific dosage adjustment guidelines in patients with hepatic impairment are not available. Hepatic function should be monitored before and during treatment with dapsone.
Extemporaneous oral suspension: Shake well before administering. Measure dosage with calibrated measuring device. Add a small amount of vehicle mixture of Ora-Plus and Ora-Sweet and mix to a uniform paste.
Add geometric proportions of vehicle to almost desired volume while continuing to mix then transfer to graduated cylinder. Rinse mortar and pestle with vehicle and transfer to graduated cylinder. Add enough vehicle to bring the final volume to mL.
Storage: The oral suspension is stable for 90 days when stored at room temperature or refrigerated. Before applying topical formulations of dapsone, gently cleanse affected area with a mild soap and pat skin dry. Gel Formulation: Apply a thin layer to the acne affected area as directed. Rub the gel into the skin gently and completely.
Aczone gel is gritty with visible drug substance particles present. Wash hands immediately after applying. Generic: - Protect from light - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F Aczone: - Protect from freezing - Store at controlled room temperature between 68 and 77 degrees F. Dapsone should be used with caution in cases of severe anemia, G6PD deficiency glucose 6-phosphate dehydrogenase deficiency or methemoglobin reductase deficiency because hemolytic anemia can occur.
The safety of dapsone topical gel Ac zone was evaluated in a randomized, double-blind, cross-over study of 64 patients with G6PD deficiency and acne vulgaris. After 2 weeks, a mean decline of 0. The study found no evidence of clinically significant hemolytic anemia following application of dapsone topical gel. Laboratory changes suggestive of mild hemolysis were noted in some subjects. Glucose 6-phosphate dehydrogenase levels should be obtained in all patients before using systemically administered dapsone.
Baseline complete blood counts, including a reticulocyte count, should be obtained in patients who are G6PD deficient or with a history of anemia. Routine follow-up for complete blood count and reticulocyte count should be implemented for patients at risk. Toxic hepatitis, cholestatic jaundice, and hyperbilirubinemia have been reported during the initial stages of systemic dapsone treatment. Periodic monitoring of liver-function tests is recommended. Dapsone should be used cautiously in patients with preexisting hepatic disease.
Uncontrolled studies of systemic dapsone use in pregnant women have not demonstrated fetal risk during any trimester of pregnancy nor did use affect reproduction capacity. Although further study is needed, it has been recommended by some authorities that dapsone therapy be maintained during pregnancy in cases of leprosy or dermatitis herpetiformis.
Information on the use of topical dapsone in pregnant patients is not available; however, systemic exposure of the topical gel is low compared to oral dapsone administration approximately times less. Dapsone is distributed into breast milk in large quantities after oral dosing and can cause hemolytic anemia in nursing infants with G6PD deficiency.
Absorption after topical administration is minimal relative to oral dapsone administration. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.
If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Oral dapsone can be used safely in pediatric patients i. Administer dapsone, a synthetic sulfone, with caution in patients with sulfonamide hypersensitivity. It may be prudent to monitor patients for allergic-type reactions when initiating dapsone.
Although structurally it contains an aromatic amine known to trigger adverse reactions at position N4, dapsone does not contain the N1-moiety that is present in sulfonamide antibiotics and thought to be responsible for hypersensitivity-type adverse reactions.
The risk of cross-sensitivity in patients taking a nonantibiotic sulfonamide that have a history of sulfonamide hypersensitivity is low and has been confirmed by observational studies.
In general, patients with a history of hypersensitivity to any drug are predisposed for subsequent hypersensitivity reactions to other drugs. Because of this, patients with a history of sulfonamide hypersensitivity should be monitored for hypersensitivity reactions to other drugs, including dapsone; however, treatment with a nonantibiotic sulfonamide may not need to be withheld in patients with a sulfonamide allergy as long as patients are monitored appropriately, especially if alternative therapies are not available.
Acetaminophen: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia. Acetaminophen; Aspirin, ASA; Caffeine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Acetaminophen; Aspirin: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Aspirin; Diphenhydramine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Caffeine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Acetaminophen; Caffeine; Dihydrocodeine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Caffeine; Pyrilamine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. As dapsone is not associated with renal vasculitis, rifampicin toxicity might be considered an explanation of the kidney histopathology.
However, rifampicin is most commonly cited as a drug causing tubulo-interstitial lesions, with eosinophilic and mononuclear cellular infiltration [8]. Furthermore, since the patient was subsequently treated with a six-month course of rifampicin for tuberculosis without any adverse reactions, the possibility of rifampicin-induced renal toxicity seems unlikely.
This patient exemplifies a serious dapsone reaction. Aggressive immune-suppressive therapy was used because of the severe renal failure; this therapy had a favorable outcome. Since dapsone is widely used for leprosy and other diseases, such as dermatitis herpetiformis, acne vulgaris, psoriasis, and Pneumocystis carinii pneumonia in acquired immunodeficiency syndrome, clinicians should be made aware of this life-threatening reaction.
Correspondence to Dr. Open menu Brazil. Brazilian Journal of Infectious Diseases. Open menu. Text EN Text English. Leprosy; dapsone syndrome; acute renal failure. Key Words : Leprosy, dapsone syndrome, acute renal failure. Case Report A year-old female, recently diagnosed with indeterminate leprosy, was prescribed mg rifampicin monthly and mg dapsone daily.
Discussion Dapsone has been used for over 40 years for the treatment of a variety of conditions, and it is the most widely-used drug for leprosy treatment. Cor J F Fontes. Lau G. A fatal case of drug-induced multi-organ damage in a patient with Hansen's disease: dapsone syndrome or rifampicin toxicity? Forensic Sci Int ; Some of those were related not only to the variability of the acetylators but also to the dose and the modality of treatment [ 1 , 4 , 6 , 8 ].
This wide variability of the latency period suggests a multi-organ hypersensitivity reaction, but the exact mechanisms are unclear and reviewed later [ 4 — 7 ].
The classic triad of DHS consists of fever, eruption, and internal organ involvement Table 3. Fever, hepatitis, exfoliative dermatitis, adenopathy and hemolytic anemia might be seen in varying combinations and sequences [ 9 ].
While traditionally a hepatitis or transaminitis is seen, cholangitis has also been described as a component of the DHS [ 9 ]. Studies have shown that this syndrome may begin as early as 7—10 days after administration of the drug or as late as 6 months into therapy with dapsone. Cutaneous lesions can range from erythematous papules as in our patient, to plaques, pustules, and eczematous lesions [ 1 , 3 — 8 ]. The severity of the cutaneous changes does not correlate with the severity or extent of internal organ involvement which may remain asymptomatic of even life-threatening [ 10 ].
Cutaneous lesions usually begin to resolve 2 weeks after stopping therapy. Some patients may also develop severe dermatitis and complications, such as the Steven Johnson Syndrome or toxic epidermal necrolysis Table 1. These patients may experience prolonged morbidity and even mortality with the complications. Especially in severe cases, malnutrition, protein loss and secondary infection may complicate the illness, and these patients need to be monitored for complications more aggressively.
In traditional DHS , antibiotics have little or no role unless obvious infection, cellulitis or sepsis is present. Infiltrative lung disease is the most common pattern of drug-induced injury [ 10 ].
This pattern can cause interstitial lung damage, alveolar damage or vasculitic involvement e. As listed in Table 3 , DHS can also involve the lung, with 10 cases reported in the literature.
In the patient described by us, pulmonary infiltrates and pleural effusions with severe hypoxemia were present suggesting interference with alveolocapillary oxygen transfer. Other manifestations have also been described in the literature. Table 4 summarizes the different pulmonary manifestations of dapsone. Pulmonary manifestations of the DHS are sometimes dominant features, as occurred in our patient.
Manifestations have included the development of eosinophilic pneumonia [ 11 — 15 ], hypersensitivity pneumonia [ 16 ], pleural effusion [ 17 ]. Many reported cases of eosinophilic pneumonia have an associated systemic blood eosinophilia, which however, was not present in our case. The rapid clinical deterioration seen with DHS can lead to respiratory failure as seen in our patient and sometimes death, if untreated or unrecognized.
Other manifestations of this syndrome include hepato-biliary dysfunction such as jaundice[ 1 ], hepatomegaly [ 1 ]and cholangitis [ 9 ], splenomegaly[ 1 ], eosinophilia[ 1 , 13 ], photosensitivity[ 1 ], elevated sedimentation rate [ 1 ], and a mononucleosis picture that can mimic EBV and CMV infection [ 1 , 7 ]. In addition, DHS can include peripheral neuropathy [ 18 ], psychosis [ 19 ], renal involvement such as nephrotic syndrome [ 1 ] and renal papillary necrosis [ 20 ] and pancreatitis [ 17 ] as found in our patient.
As listed in Table 3 , a maculopapular eruption, bullous disease, photosensitivity and oral erosions can occur. The differential diagnosis of multisystem illness presenting in a patient on dapsone is shown in Table 5. These include diseases such as: DRESS syndrome and its variants, vasculitis Churg Strauss syndrome , Hypereosinophilic syndrome, TENS Toxic epidermal necrolysis syndrome , Steven Johnson Syndrome, Still's disease, Hematological disorders leukemia, lymphoma , paraneoplastic disorders and certain connective tissue disorders.
We will discuss a few of these important conditions in this section. In the case of the latter, drug rash, eosinophilia and systemic symptoms are often present. DRESS syndrome can be seen with a variety of medications, including anticonvulsants, sulfonamides, allopurinol, calcium channel blockers, NSAIDS Non-steroidal anti-inflammatory drugs and dapsone [ 21 ].
Fever, skin eruption, adenopathy, eosinophilia and internal organ involvement might also be seen [ 21 ]. It is important to note, that both disorders may overlap. A prodromal phase, similar to a flu-like illness, lasting up to14 days, may precede the skin eruption. The acute phase of TENS consists of persistent fevers, generalized epidermal sloughing and mucous membrane involvement [ 22 ]. Cutaneous vasculitis which can be part of a systemic disease needs also to be excluded. The evaluation of such patients needs a complete work-up for the presence of systemic disease.
Skin biopsy and immunofluorescence studies may also helpful in the diagnosis of cutaneous vasculitis in which immunoglobulin and complement deposition are found [ 23 ]. If dermatitis and pulmonary disease is the dominant feature, necrotizing vasculitides and Churg Strauss syndrome needs to be excluded. If dermatological manifestations dominate the presentation, with or without mucosal involvement, Steven Johnson Syndrome and TENS need to be excluded.
In some patients with a dominant eosinophilia and pulmonary infiltration, PIE syndrome [ 10 ] needs to be excluded. Laboratory tests can include a complete blood count and differential, comprehensive chemistry profile, sedimentation rate, urine analysis, arterial blood gases and a chest roentgenogram.
However, the results of treatment effects for various conditions, even dermatologic diseases, are controversial, and properly controlled trials to prove the effects and safety compared to other drugs are lacking.
Therefore, to date, this drug has been recommended as one of several treatment options for refractory chronic inflammatory conditions based on previously reported case reports or literature reviews. Regarding IgAV, Lee et al. Lee et al. It is important for clinicians to acknowledge and consider the negative effects of dapsone, including methemoglobinemia, hemolysis, agranulocytosis, various skin eruptions, and neurologic side effects such as peripheral neuropathy with primarily motor function loss, gastrointestinal symptoms, toxic or cholestatic hepatitis, and hypersensitivity syndrome; some of these effects are dose-independent [ 8 - 10 ].
Dapsone must be used with cautious in patients with glucosephosphate dehydrogenase deficiency, pulmonary diseases, heart failure, severe hepatopathy, and comedication with methemoglobinemia-inducing drugs [ 6 ].
Therefore, before drug initiation, routine evaluations including complete blood count, liver enzymes, urinalysis, and serologic tests for hepatitis, methemoglobinemia, and glucosephosphate dehydrogenase are recommended[ 6 ]. As shown by Lee et al. Thus, clinicians and their patients are at risk of experiencing serious side effects such as agranulocytosis or hypersensitivity syndrome when dapsone therapy is used repeatedly.
In conclusion, the paper by Lee et al. However, clinicians should be aware of both treatment effects and controversies related to dapsone therapy and consider its benefits and risks.
❾-50%}Dapsone renal failure.Dapsone syndrome with acute renal failure during leprosy treatment: case report
The finding of secondary membranous nephropathy MN was unexpected as to date there has not been any reports of renal disease and EDD. We report a case of secondary MN in a patient with EDD now undergoing a full malignancy investigation. The webpage has been translated to. The ASN website can be translated into a number of different languages. For more information view the disclaimer. This site requires javascript, which you do not appear to have enabled.
In order for everything to function properly, please enable javascript. ASN's Mission To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.
Kidney Week. Abstract: PUB Almost all patients 24 patients, Based on those findings, the authors suggested that dapsone affected refractory IgAV. Dapsone is an aniline derivative belonging to the group of synthetic sulfones [ 6 ]. Because of its antimycobacterial, antiprotozoal, and anti-inflammatory effects, dapsone has been used as a first-line or adjunctive therapy for chronic inflammatory dermatoses such as leprosy, chronic urticaria, cutaneous lupus erythematosus, and IgA pemphigus [ 7 ].
It has also been used to treat nondermatological diseases such as rheumatoid arthritis, immune thrombocytopenia, stroke, seizure disorder, and glioblastoma [ 6 ]. Considering that patients with chronic inflammatory conditions frequently need steroids to achieve disease control, dapsone may be a useful and attractive option for those patients, especially pediatric patients who are vulnerable to the side effects of steroids. However, the results of treatment effects for various conditions, even dermatologic diseases, are controversial, and properly controlled trials to prove the effects and safety compared to other drugs are lacking.
Therefore, to date, this drug has been recommended as one of several treatment options for refractory chronic inflammatory conditions based on previously reported case reports or literature reviews. Regarding IgAV, Lee et al. Lee et al. It is important for clinicians to acknowledge and consider the negative effects of dapsone, including methemoglobinemia, hemolysis, agranulocytosis, various skin eruptions, and neurologic side effects such as peripheral neuropathy with primarily motor function loss, gastrointestinal symptoms, toxic or cholestatic hepatitis, and hypersensitivity syndrome; some of these effects are dose-independent [ 8 - 10 ].
Dapsone must be used with cautious in patients with glucosephosphate dehydrogenase deficiency, pulmonary diseases, heart failure, severe hepatopathy, and comedication with methemoglobinemia-inducing drugs [ 6 ]. Therefore, before drug initiation, routine evaluations including complete blood count, liver enzymes, urinalysis, and serologic tests for hepatitis, methemoglobinemia, and glucosephosphate dehydrogenase are recommended[ 6 ].
As shown by Lee et al. Thus, clinicians and their patients are at risk of experiencing serious side effects such as agranulocytosis or hypersensitivity syndrome when dapsone therapy is used repeatedly. In conclusion, the paper by Lee et al. However, clinicians should be aware of both treatment effects and controversies related to dapsone therapy and consider its benefits and risks. Further studies are needed to prove the safety and effects of dapsone for refractory IgAV.
Conflicts of interest No potential conflict of interest relevant to this article was reported. Peripheral eosinophilia has been described [7].
Rifampicin, which is also used in MDT, is a strong inducer of microsomal enzymes, diminishing the pharmacological effects of a wide variety of drugs, including dapsone. Thus, any putative interaction of rifampicin predisposing to dapsone syndrome in our patient would not be a consequence of direct enhancement of dapsone toxicity [1]. Kidney involvement was unexpected. As dapsone is not associated with renal vasculitis, rifampicin toxicity might be considered an explanation of the kidney histopathology.
However, rifampicin is most commonly cited as a drug causing tubulo-interstitial lesions, with eosinophilic and mononuclear cellular infiltration [8]. Furthermore, since the patient was subsequently treated with a six-month course of rifampicin for tuberculosis without any adverse reactions, the possibility of rifampicin-induced renal toxicity seems unlikely. This patient exemplifies a serious dapsone reaction.
Aggressive immune-suppressive therapy was used because of the severe renal failure; this therapy had a favorable outcome. Since dapsone is widely used for leprosy and other diseases, such as dermatitis herpetiformis, acne vulgaris, psoriasis, and Pneumocystis carinii pneumonia in acquired immunodeficiency syndrome, clinicians should be made aware of this life-threatening reaction.
Correspondence to Dr. Open menu Brazil. Brazilian Journal of Infectious Diseases. Open menu. Text EN Text English. Leprosy; dapsone syndrome; acute renal failure.
Key Words : Leprosy, dapsone syndrome, acute renal failure. Case Report A year-old female, recently diagnosed with indeterminate leprosy, was prescribed mg rifampicin monthly and mg dapsone daily. Discussion Dapsone has been used for over 40 years for the treatment of a variety of conditions, and it is the most widely-used drug for leprosy treatment. Cor J F Fontes.
Lau G. A fatal case of drug-induced multi-organ damage in a patient with Hansen's disease: dapsone syndrome or rifampicin toxicity? Forensic Sci Int ; Richardus J. H, Smith T. Increased incidence in leprosy of hypersensitivity reactions to dapsone after introduction of multidrug therapy.
Lepr Rev ; Reeve P. Dapsone syndrome in Vanuatu: a high incidence during multidrug therapy MDT of leprosy. J Trop Med Hyg ; Saito S. A case of the 'dapsone syndrome'. Clin Exp Dermatol ;
To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.
Click an icon below to load this item into your calendar. Time zone help. Erythema elevatum diutinum EDD is a rare cutaneous small vessel vasculitis with dapsone being the drug of choice. Patient was on dapsone in the past for over 10 years, however in the last 6months was not taking any medications.
Vancomycin, zosyn and dapsone mg BID were started on admission. By day 3 only dapsone was continued as imaging was without evidence of deep infection.
On day 4 he developed AKI, creatinine Crt 4. Labs also included Hb of 8. Serum immunofixation revealed IgA-kappa in the beta region and a faint IgA-kappa monoclonal protein in the gamma region.
Autoimmune and infectious serologic work-up negative. Dapsone was stopped on day 5 and renal biopsy was performed due to ongoing rise in Crt on day 8. Biopsy confirmed diffuse active interstitial nephritis with prominent eosinophilic inflammation along with low grade membranous nephropathy favoring secondary, PLA2R negative. Patient started on IV solumedrol followed by oral prednisone taper over 6 weeks. DI-AIN was attributed to dapsone.
Despite withholding this medication, the Crt continued to rise prompting renal biopsy. Studies suggest that early corticosteroid initiation is associated with better outcomes and be considered in patients with no prior kidney dysfunction.
In patients with suspected DI-AIN where a biopsy cannot be performed, a trial of empiric steroid therapy may be considered. The finding of secondary membranous nephropathy MN was unexpected as to date there has not been any reports of renal disease and EDD. We report a case of secondary MN in a patient with EDD now undergoing a full malignancy investigation. The webpage has been translated to.
The ASN website can be translated into a number of different languages. For more information view the disclaimer. This site requires javascript, which you do not appear to have enabled. In order for everything to function properly, please enable javascript. ASN's Mission To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.
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We describe clinical and pathological features of kidney and skin involvement in a patient with hypersensitivity vasculitis associated with dapsone. We report a patient who developed acute renal failure, as well as other complications characteristic of dapsone syndrome, during leprosy treatment. Dapsone is an antibacterial medication used in the treatment of dermatitis herpetiformis (a skin condition) and leprosy (Hansen's disease). A 4-yr-old Middle-Eastern female with h/o Jeune syndrome, end stage renal disease, s/p renal transplant with chronic rejection on immunosuppressive therapy was. We describe clinical and pathological features of kidney and skin involvement in a patient with hypersensitivity vasculitis associated with dapsone. Subsequent laboratory investigations showed a lowering of hemoglobin levels, with a positive Coombs direct test.Send the page " " to a friend, relative, colleague or yourself. We do not record any personal information entered above. Synthetic sulfone chemically similar to sulfonamides Has antiinfective and immunosuppressive properties Agent of choice for all forms of leprosy; used for PCP prophylaxis; used in combination with pyrimethamine for prevention of toxoplasmosis in AIDS patients; used for various dermatologic disorders and topically for acne.
Maintenance dosage is usually 25 to mg daily. The lowest effective dose should be used as soon as possible.
The dose may be increased if the symptoms are not completely controlled. Apply a thin layer topically to acne affected areas twice daily; if no improvement after 12 weeks, reassess appropriateness of dapsone therapy.
Apply a thin layer topically to the entire face once daily. In addition, a thin layer may be applied topically to other acne affected areas once daily. Reassess appropriateness of dapsone therapy if no improvement after 12 weeks. Consider prophylaxis for infants born to HIV-infected mothers beginning at 4 to 6 weeks. Discontinue prophylaxis in infants with indeterminate HIV infection status when they are determined to be definitively ore presumptively HIV-uninfected.
Do not discontinue prophylaxis in HIV-infected infants younger than 12 months. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs.
Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.
Duration of prophylaxis for ALL is from induction to the end of maintenance. Recommended for patients receiving alemtuzumab or corticosteroids at doses equivalent to more than 0. Prophylaxis is recommended for patients with AML and solid tumors for the duration of chemotherapy. HIV-infected infants and infants whose infection status remains unknown should continue to receive prophylaxis for the first year of life.
A dose of mg PO once daily, increasing the dose by 50 mg every 1 to 2 weeks until remission occurs has been used. Subsequently, reduce dosage to lowest effective maintenance dose. Maximum oral dosage information not established; safety and efficacy of topical gel not established. Dapsone can cause toxic hepatitis and cholestatic jaundice, however, specific dosage adjustment guidelines in patients with hepatic impairment are not available.
Hepatic function should be monitored before and during treatment with dapsone. Extemporaneous oral suspension: Shake well before administering. Measure dosage with calibrated measuring device. Add a small amount of vehicle mixture of Ora-Plus and Ora-Sweet and mix to a uniform paste. Add geometric proportions of vehicle to almost desired volume while continuing to mix then transfer to graduated cylinder. Rinse mortar and pestle with vehicle and transfer to graduated cylinder.
Add enough vehicle to bring the final volume to mL. Storage: The oral suspension is stable for 90 days when stored at room temperature or refrigerated. Before applying topical formulations of dapsone, gently cleanse affected area with a mild soap and pat skin dry.
Gel Formulation: Apply a thin layer to the acne affected area as directed. Rub the gel into the skin gently and completely. Aczone gel is gritty with visible drug substance particles present. Wash hands immediately after applying. Generic: - Protect from light - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F Aczone: - Protect from freezing - Store at controlled room temperature between 68 and 77 degrees F. Dapsone should be used with caution in cases of severe anemia, G6PD deficiency glucose 6-phosphate dehydrogenase deficiency or methemoglobin reductase deficiency because hemolytic anemia can occur.
The safety of dapsone topical gel Ac zone was evaluated in a randomized, double-blind, cross-over study of 64 patients with G6PD deficiency and acne vulgaris. After 2 weeks, a mean decline of 0. The study found no evidence of clinically significant hemolytic anemia following application of dapsone topical gel.
Laboratory changes suggestive of mild hemolysis were noted in some subjects. Glucose 6-phosphate dehydrogenase levels should be obtained in all patients before using systemically administered dapsone. Baseline complete blood counts, including a reticulocyte count, should be obtained in patients who are G6PD deficient or with a history of anemia.
Routine follow-up for complete blood count and reticulocyte count should be implemented for patients at risk. Toxic hepatitis, cholestatic jaundice, and hyperbilirubinemia have been reported during the initial stages of systemic dapsone treatment.
Periodic monitoring of liver-function tests is recommended. Dapsone should be used cautiously in patients with preexisting hepatic disease. Uncontrolled studies of systemic dapsone use in pregnant women have not demonstrated fetal risk during any trimester of pregnancy nor did use affect reproduction capacity.
Although further study is needed, it has been recommended by some authorities that dapsone therapy be maintained during pregnancy in cases of leprosy or dermatitis herpetiformis. Information on the use of topical dapsone in pregnant patients is not available; however, systemic exposure of the topical gel is low compared to oral dapsone administration approximately times less.
Dapsone is distributed into breast milk in large quantities after oral dosing and can cause hemolytic anemia in nursing infants with G6PD deficiency. Absorption after topical administration is minimal relative to oral dapsone administration.
Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.
If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA. Oral dapsone can be used safely in pediatric patients i. Administer dapsone, a synthetic sulfone, with caution in patients with sulfonamide hypersensitivity. It may be prudent to monitor patients for allergic-type reactions when initiating dapsone. Although structurally it contains an aromatic amine known to trigger adverse reactions at position N4, dapsone does not contain the N1-moiety that is present in sulfonamide antibiotics and thought to be responsible for hypersensitivity-type adverse reactions.
The risk of cross-sensitivity in patients taking a nonantibiotic sulfonamide that have a history of sulfonamide hypersensitivity is low and has been confirmed by observational studies.
In general, patients with a history of hypersensitivity to any drug are predisposed for subsequent hypersensitivity reactions to other drugs. Because of this, patients with a history of sulfonamide hypersensitivity should be monitored for hypersensitivity reactions to other drugs, including dapsone; however, treatment with a nonantibiotic sulfonamide may not need to be withheld in patients with a sulfonamide allergy as long as patients are monitored appropriately, especially if alternative therapies are not available.
Acetaminophen: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia. Acetaminophen; Aspirin, ASA; Caffeine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Acetaminophen; Aspirin: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Aspirin; Diphenhydramine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Caffeine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Acetaminophen; Caffeine; Dihydrocodeine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Acetaminophen; Caffeine; Pyrilamine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Chlorpheniramine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Acetaminophen; Chlorpheniramine; Dextromethorphan: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Chlorpheniramine; Phenylephrine : Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Codeine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Dextromethorphan: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Acetaminophen; Dextromethorphan; Doxylamine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Acetaminophen; Dextromethorphan; Phenylephrine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Dextromethorphan; Pseudoephedrine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Dichloralphenazone; Isometheptene: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Acetaminophen; Diphenhydramine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Guaifenesin; Phenylephrine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Acetaminophen; Hydrocodone: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Oxycodone: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Acetaminophen; Pamabrom; Pyrilamine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Pentazocine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Propoxyphene: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia. Acetaminophen; Pseudoephedrine: Moderate Coadministration of dapsone with acetaminophen may increase the risk of developing methemoglobinemia.
Amprenavir: Minor Amprenavir may inhibit the metabolism of other medications that are metabolized via cytochrome P 3A4 including dapsone. Although drug interaction studies have not been conducted, the serum concentrations of dapsone may be increased with concomitant administration of amprenavir.
Amyl Nitrite: Moderate Coadministration of dapsone with nitrates may increase the risk of developing methemoglobinemia. Apalutamide: Moderate Monitor for an increase in hemolysis if coadministration of dapsone with apalutamide is necessary; dapsone efficacy may also be compromised.
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