Cutaneous reactions during treatment with Nifurtimox or Benznidazole among Trypanosoma cruzi seropositive adults without symptomatic cardiomyopathy: A safety sub analysis of a placebo‐controlled randomised trial

Figures

• 

  FIGURE 1. Frequency of skin adverse reactions reported in studies of patients receiving Benznidazole (see references in the appended list).Górgolas 2013: The use of steroids to prevent cutaneous reactions to Benznidazole in patients with Chagas disease.C.A. Morillo 2015: Rationale and design of a randomised placebo‐controlled trial assessing the effects of etiologic treatment in Chagas' cardiomyopathy: The BENznidazole Evaluation For Interrupting Trypanosomiasis (BENEFIT).Israel Molina 2014: Randomised trial of Posaconazole and Benznidazole for chronic Chagas' disease. Chagasazol.Hasslocher‐Moreno 2012: Safety of benznidazole use in the treatment of chronic Chagas' disease.Bartolomé Carrilero 2011: Efectos secundarios del tratamiento con Benznidazol en una cohorte de pacientes con enfermedad de Chagas en un país no endémico.A. Pérez‐Ayala 2010: Chagas disease in Latin American migrants: A Spanish challenge.Tomheim 2013: Improved completion rates and characterization of drug reactions with an intensive Chagas disease treatment programme in rural Bolivia.Salvador 2015: Evaluation of cytokine profile and HLA association in Benznidazole related cutaneous reactions in patients with Chagas…

• 

  FIGURE 2. Randomised treatment allocation (above), where participants received their study medications at the start and 60 days later. Those assigned to 60 days of active treatment are given placebo for the other 60 days as per random allocation. Below: Daily treatment schedule using capsules of similar appearance across study groups.

• 

  FIGURE 3. Incidence of skin reactions after treatment (SKRAT) in the study groups. Light and dark blue bars indicate moderate or severe SKRAT, respectively. Above: SKRAT by agent (left) or treatment regime (right). Below: SKRAT across study groups. See description in the text.

• 

  FIGURE 4. Dermatological lesions and descriptions: 1. Scaly plaques: 1a. Plaques with irregular and active borders, accompanied by visible scaling. 1b. Erythematous plaque with a scaly surface and keratosis. 2. Erythematous lesions: Red, linear lesions prominently present over the skin folds. 3. Urticarial lesions: Lesions presenting as wheals similar to those of urticaria, with dermographism. 4. Keratoderma: Thickening of the skin on the sole of the foot, with abundant scaling and the presence of excoriation. 5. Papules and pustules: Multiple papules and pustules that cluster together forming a macule with a reddish background. 6. Maculopapular exanthem: 6a. Skin eruption consisting of spots and small papules distributed on the trunk. 6b. Disseminated maculopapular rash converging into a macule with an erythematous background in the central trunk region and presenting excoriations.

• 

  FIGURE 5. Symptoms at presentation of skin reactions after treatment by study groups. [Correction added on 17 June 2025, after first online publication: In Figure 5, the legend ‘NFX’ has been added to the second image on the top right.]

• 

  FIGURE 6. Distribution of skin reactions after treatment (SKRAT) seen during the follow‐up study visits by treatment groups. Each row represents a participant reported with SKRAT within each group. The light and dark blue cells represent SKRAT judged as moderate or severe, respectively. The grey cells represent a SKRAT while receiving placebo. For the 60CD groups, the study visits were re‐ordered so the active treatment period is shown first in this figure. 120HD: 120‐day treatment using half of the standard doses (Benznidazole 150 mg/day or Nifurtimox 240 mg/day); 60CD: 60‐day treatment using conventional doses (Benznidazole 300 mg/day or Nifurtimox 480 mg/day).