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Fatal outcome of immune reconstitution inflammatory syndrome in a patient with AIDS-associated Kaposi sarcoma
Med Clin (Barc). 2015;145(12):551–555
www.elsevier.es/medicinaclinica
Letters to the Editor Fatal outcome of immune reconstitution inflammatory syndrome in a patient with AIDS-associated Kaposi sarcoma夽 Síndrome de reconstitución inmunitaria en un caso de sarcoma de Kaposi asociado a sida con desenlace mortal Dear Editor, The incidence of AIDS-associated Kaposi sarcoma (AIDS-KS) has decreased dramatically in recent years as a result of the widespread use of highly active antiretroviral therapy (HAART). There is a potential worsening or appearance of AIDS-KS with the onset of HAART despite the paradoxical improvement in immune function. This process is called immune reconstitution inflammatory syndrome associated with Kaposi sarcoma (KS-IRIS), of which there are about 50 cases reported in medical literature.1 We report a case of AIDS-KS with torpid evolution due to KS-IRIS. It is a 22-year-old male diagnosed with infection by the human immunodeficiency virus (HIV), classified as a category A3 according to the CDC system and with AIDS-KS lesions. One month after starting HAART with emtricitabine, tenofovir and efavirenz, the patient showed rapid improvement in immune function and a paradoxical worsening of AIDS-KS. Previous injuries increased in size and new skin (Fig. 1A and B), oropharyngeal and digestive injures appeared. Therefore, he was diagnosed with KS-IRIS. Because of a refractory thrombocytopenia, the patient could not be administered doxorubicin for the treatment of AIDS-KS. The patient showed
a nosocomial pneumonia that required admission to ICU. During hospitalization AIDS-KS injuries gradually increased in size, now accompanied by purpura (Fig. 1C), and facial swelling was becoming more evident. Subsequently, there was a multi-organ failure that caused the patient’s death. AIDS-KS is distinctive of AIDS and may be the first manifestation in these patients in 15% cases.2 In 1994 Chang et al. identified HHV8 as a causative agent, although recently it has been believed that HIV infection may have a role in the development of KS through the action of the transcription-transactivating protein.3 The AIDS Clinical Trials Group Oncology Committee4 published the criteria for the evaluation of AIDS-KS, considering, as high risk factors, any of the following: tumor-associated edema or ulceration, extensive oral disease, gastrointestinal KS or in other viscera, CD4 < 150/mm3 , history of opportunistic infection, thrush, symptoms B or Karnofsky index <70. The patient reported 4 high risk factors: tumor-associated edema or ulceration, extensive oral disease, visceral involvement and CD4 < 150/l. Patients treated with HAART where KS appears have a less aggressive disease compared to those who did not undergo HAART,5 as in this case. The vast majority of patients have skin lesions only, and, if visceral involvement, it is usually gastrointestinal and in lung. The firstline treatment is HAART (a protease inhibitor should be included) and it can be combined with different local therapies.5 The use of chemotherapy has been indicated in diffuse mucocutaneous involvement, visceral involvement, large extension (>25 lesions) or rapid progression.5 First-line chemotherapy is PEGylated liposomal doxorubicin 20 mg/m2 intravenously every 2 weeks or
Fig. 1. (A and B) Images of worsening of Kaposi sarcoma a month after starting highly active antiretroviral therapy. Increasing number and size of injuries of AIDS-associated Kaposi sarcoma. (C) Images, during admission to the Intensive Care Unit, of the continuing Kaposi sarcoma worsening. Increased volume of AIDS-associated Kaposi sarcoma injuries and appearance of purpura due to thrombocytopenia.
夽 Please cite this article as: Melé-Ninot G, Sola-Ortigosa J, Iglesias-Sancho M, DelásAmat J. Síndrome de reconstitución inmunitaria en un caso de sarcoma de Kaposi asociado a sida con desenlace mortal. Med Clin (Barc). 2015;145:551–552. ˜ S.L.U. All rights reserved. 2387-0206/© 2015 Elsevier Espana,
552
Letters to the Editor / Med Clin (Barc). 2015;145(12):551–555
daunorubicin citrate liposome 40 mg/m2 intravenously every 2 weeks. Paclitaxel has been indicated only for patients with recurrence or refractory to first-line chemotherapy.5 HAART causes partial or complete AIDS-KS injury resolution in 55–60%,6 but there is a risk of KS-IRIS. KS-IRIS is an inflammatory process in which there is paradoxically a temporary relationship between the onset of HAART, the onset or progression of AIDSKS and improved immune status evidenced by a decreased viral load and increased CD4 count.7 KS patients with low basal CD4 count appear to have increased risk of KS-IRIS,8,9 rapid increased CD4 count during HAART onset,10 high viral load of HIV,9 edema associated,10 KS present clinically prior to HAART, HHV8 detectable in plasma and hematocrit >30%.7 Corticosteroids are not recommended because they would promote HHV8 and growth factor replication. Thus, KS would be worsened.7 KS early identification and previous or combined use of chemotherapy with HAART appears to be the most effective procedure to prevent the consequences of KS-IRIS7 and reduce mortality.1 In conclusion, it is important to understand this entity, and not to be confused with a failure of HAART, and know it does not imply a change of antiretroviral therapy, except in cases with potential irreversible damage.7
2. Avilés Izquierdo JA, García-Andrade CR, Gómez-Cornejo LP, Lazaro Ochaíta P, de Portugal Alvarez J. Characteristics of Kaposi’s sarcoma: a retrospective study in a reference hospital. An Med Interna. 2003;20:170–4 [Spanish]. 3. Daly ML, Fogo A, McDonald C, Morris-Jones R. Kaposi sarcoma: no longer an AIDS-defining illness? A retrospective study of Kaposi sarcoma cases with CD4 counts above 300/mm3 at presentation. Clin Exp Dermatol. 2014;39: 7–12. 4. Krown SE, Testa MA, Huang J. AIDS-related Kaposi’s sarcoma: prospective validation of the AIDS Clinical Trials Group staging classification. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol. 1997;15:3085–92. 5. La Ferla L, Pinzone MR, Nunnari G, Martellotta F, Lleshi A, Tirelli U, et al. Kaposi’s sarcoma in HIV-positive patients: the state of art in the HAART-era. Eur Rev Med Pharmacol Sci. 2013;17:2354–65. 6. Connick E, Kane MA, White IE, Ryder J, Campbell TB. Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma during potent antiretroviral therapy. Clin Infect Dis. 2004;39:1852–5. 7. Stover KR, Molitorisz S, Swiatlo E, Muzny CA. A fatal case of Kaposi sarcoma due to immune reconstitution inflammatory syndrome. Am J Med Sci. 2012;343:421–5. 8. Lacombe JM, Boue F, Grabar S, Viget N, Gazaignes S, Lascaux-Cametz AS, et al. Risk of Kaposi sarcoma during the first months on combination antiretroviral therapy. AIDS. 2013;27:635–43. 9. Feller L, Anagnostopoulos C, Wood NH, Bouckaert M, Raubenheimer EJ, Lemmer J. Human immunodeficiency virus-associated Kaposi sarcoma as an immune reconstitution inflammatory syndrome: a literature review and case report. J Periodontol. 2008;79:362–8. 10. Bower M, Nelson M, Young AM, Thirlwell C, Newsom-Davis T, Mandalia S, et al. Immune reconstitution inflammatory syndrome associated with Kaposi’s sarcoma. J Clin Oncol. 2005;23:5224–8.
Conflict of interests
Gemma Melé-Ninot a,∗ , Joaquim Sola-Ortigosa a , Maribel Iglesias-Sancho a , Jordi Delás-Amat b
The authors report no conflict of interest in drafting the manuscript. References 1. Letang E, Lewis JJ, Bower M, Mosam A, Borok M, Campbell TB, et al. Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma: higher incidence and mortality in Africa than in the UK. AIDS. 2013;27: 1603–13.
Gastroparesis: An under-recognized complication after atrial fibrillation catheter ablation procedure夽 Gastroparesia: una complicación poco reconocida de la ablación percutánea de la fibrilación auricular Dear Editor, Percutaneous ablation of atrial fibrillation (AF) is an increasingly common treatment in daily clinical practice. In a recent European study incidence of complications secondary to catheter ablation of atrial fibrillation was 7.7%,1 being cardiovascular complications (mainly pericarditis) the most frequently reported. Among gastrointestinal complications, only one case of esophageal ulcer was reported. However, some cases of gastroparesis have been exceptionally described in the medical literature and its approach has not been established. We report 2 cases of gastroparesis after percutaneous ablation of AF. Both patients had symptomatic AF and refractory to antiarrhythmic therapy. Both of them underwent percutaneous ablation
夽 Please cite this article as: Calvo N, García de Yébenes-Castro M, Arguedas H, García-Bolao I. Gastroparesia: una complicación poco reconocida de la ablación percutánea de la fibrilación auricular. Med Clin (Barc). 2015;145:552–553.
a
Servicio de Dermatología, Hospital Universitari Sagrat Cor, Barcelona, Spain b Servicio de Medicina Interna, Hospital Universitari Sagrat Cor, Barcelona, Spain ∗ Corresponding author. E-mail address: [email protected] (G. Melé-Ninot).
of AF consisting of the circumferential isolation of pulmonary veins using non-fluoroscopic electroanatomic mapping system. Radiofrequency was used in both cases as an energy source, with an irrigated catheter with a temperature up to 40 ◦ C and a maximum power of 35 W. The procedure was performed without any complications and the patients were discharged after 24 h. A few days later the patients came to our center with symptoms of dyspnea, feeling of gastric fullness and epigastric pain. They underwent a CT scan and the presence of gastro-esophageal fistula was ruled out, but the CT showed a significant gastric dilation with food remains. Patients underwent an endoscopic study, which revealed small superficial erosions in the esophagus, and a study of gastric emptying, which showed gastric hypomotility. Treatment was initiated with prokinetic agents, proton-pump inhibitors and NPO. The symptoms were subsiding and oral diet was reintroduced with good tolerance after 3 days. Patients remain asymptomatic more than 12 months after ablation. In this paper we describe a poorly defined extracardiac complication of catheter ablation of atrial fibrillation caused by vagus nerve injury. To date, only a few cases of gastroparesis have been reported after using radiofrequency during percutaneous ablation of AF.2 The vagus nerve runs down and borders both sides of esophagus and trachea. The vagus nerve joins the sympathetic fibers at the back of the left atrium, forming a nerve plexus. In most cases, this plexus is located behind the right inferior pulmonary vein.3 Caudally, the vagus nerve is divided into two branches responsible for the innervation of the upper part of the digestive tract, controlling gastric motility and pylorus.4 Because of
www.elsevier.es/medicinaclinica
Letters to the Editor Fatal outcome of immune reconstitution inflammatory syndrome in a patient with AIDS-associated Kaposi sarcoma夽 Síndrome de reconstitución inmunitaria en un caso de sarcoma de Kaposi asociado a sida con desenlace mortal Dear Editor, The incidence of AIDS-associated Kaposi sarcoma (AIDS-KS) has decreased dramatically in recent years as a result of the widespread use of highly active antiretroviral therapy (HAART). There is a potential worsening or appearance of AIDS-KS with the onset of HAART despite the paradoxical improvement in immune function. This process is called immune reconstitution inflammatory syndrome associated with Kaposi sarcoma (KS-IRIS), of which there are about 50 cases reported in medical literature.1 We report a case of AIDS-KS with torpid evolution due to KS-IRIS. It is a 22-year-old male diagnosed with infection by the human immunodeficiency virus (HIV), classified as a category A3 according to the CDC system and with AIDS-KS lesions. One month after starting HAART with emtricitabine, tenofovir and efavirenz, the patient showed rapid improvement in immune function and a paradoxical worsening of AIDS-KS. Previous injuries increased in size and new skin (Fig. 1A and B), oropharyngeal and digestive injures appeared. Therefore, he was diagnosed with KS-IRIS. Because of a refractory thrombocytopenia, the patient could not be administered doxorubicin for the treatment of AIDS-KS. The patient showed
a nosocomial pneumonia that required admission to ICU. During hospitalization AIDS-KS injuries gradually increased in size, now accompanied by purpura (Fig. 1C), and facial swelling was becoming more evident. Subsequently, there was a multi-organ failure that caused the patient’s death. AIDS-KS is distinctive of AIDS and may be the first manifestation in these patients in 15% cases.2 In 1994 Chang et al. identified HHV8 as a causative agent, although recently it has been believed that HIV infection may have a role in the development of KS through the action of the transcription-transactivating protein.3 The AIDS Clinical Trials Group Oncology Committee4 published the criteria for the evaluation of AIDS-KS, considering, as high risk factors, any of the following: tumor-associated edema or ulceration, extensive oral disease, gastrointestinal KS or in other viscera, CD4 < 150/mm3 , history of opportunistic infection, thrush, symptoms B or Karnofsky index <70. The patient reported 4 high risk factors: tumor-associated edema or ulceration, extensive oral disease, visceral involvement and CD4 < 150/l. Patients treated with HAART where KS appears have a less aggressive disease compared to those who did not undergo HAART,5 as in this case. The vast majority of patients have skin lesions only, and, if visceral involvement, it is usually gastrointestinal and in lung. The firstline treatment is HAART (a protease inhibitor should be included) and it can be combined with different local therapies.5 The use of chemotherapy has been indicated in diffuse mucocutaneous involvement, visceral involvement, large extension (>25 lesions) or rapid progression.5 First-line chemotherapy is PEGylated liposomal doxorubicin 20 mg/m2 intravenously every 2 weeks or
Fig. 1. (A and B) Images of worsening of Kaposi sarcoma a month after starting highly active antiretroviral therapy. Increasing number and size of injuries of AIDS-associated Kaposi sarcoma. (C) Images, during admission to the Intensive Care Unit, of the continuing Kaposi sarcoma worsening. Increased volume of AIDS-associated Kaposi sarcoma injuries and appearance of purpura due to thrombocytopenia.
夽 Please cite this article as: Melé-Ninot G, Sola-Ortigosa J, Iglesias-Sancho M, DelásAmat J. Síndrome de reconstitución inmunitaria en un caso de sarcoma de Kaposi asociado a sida con desenlace mortal. Med Clin (Barc). 2015;145:551–552. ˜ S.L.U. All rights reserved. 2387-0206/© 2015 Elsevier Espana,
552
Letters to the Editor / Med Clin (Barc). 2015;145(12):551–555
daunorubicin citrate liposome 40 mg/m2 intravenously every 2 weeks. Paclitaxel has been indicated only for patients with recurrence or refractory to first-line chemotherapy.5 HAART causes partial or complete AIDS-KS injury resolution in 55–60%,6 but there is a risk of KS-IRIS. KS-IRIS is an inflammatory process in which there is paradoxically a temporary relationship between the onset of HAART, the onset or progression of AIDSKS and improved immune status evidenced by a decreased viral load and increased CD4 count.7 KS patients with low basal CD4 count appear to have increased risk of KS-IRIS,8,9 rapid increased CD4 count during HAART onset,10 high viral load of HIV,9 edema associated,10 KS present clinically prior to HAART, HHV8 detectable in plasma and hematocrit >30%.7 Corticosteroids are not recommended because they would promote HHV8 and growth factor replication. Thus, KS would be worsened.7 KS early identification and previous or combined use of chemotherapy with HAART appears to be the most effective procedure to prevent the consequences of KS-IRIS7 and reduce mortality.1 In conclusion, it is important to understand this entity, and not to be confused with a failure of HAART, and know it does not imply a change of antiretroviral therapy, except in cases with potential irreversible damage.7
2. Avilés Izquierdo JA, García-Andrade CR, Gómez-Cornejo LP, Lazaro Ochaíta P, de Portugal Alvarez J. Characteristics of Kaposi’s sarcoma: a retrospective study in a reference hospital. An Med Interna. 2003;20:170–4 [Spanish]. 3. Daly ML, Fogo A, McDonald C, Morris-Jones R. Kaposi sarcoma: no longer an AIDS-defining illness? A retrospective study of Kaposi sarcoma cases with CD4 counts above 300/mm3 at presentation. Clin Exp Dermatol. 2014;39: 7–12. 4. Krown SE, Testa MA, Huang J. AIDS-related Kaposi’s sarcoma: prospective validation of the AIDS Clinical Trials Group staging classification. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol. 1997;15:3085–92. 5. La Ferla L, Pinzone MR, Nunnari G, Martellotta F, Lleshi A, Tirelli U, et al. Kaposi’s sarcoma in HIV-positive patients: the state of art in the HAART-era. Eur Rev Med Pharmacol Sci. 2013;17:2354–65. 6. Connick E, Kane MA, White IE, Ryder J, Campbell TB. Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma during potent antiretroviral therapy. Clin Infect Dis. 2004;39:1852–5. 7. Stover KR, Molitorisz S, Swiatlo E, Muzny CA. A fatal case of Kaposi sarcoma due to immune reconstitution inflammatory syndrome. Am J Med Sci. 2012;343:421–5. 8. Lacombe JM, Boue F, Grabar S, Viget N, Gazaignes S, Lascaux-Cametz AS, et al. Risk of Kaposi sarcoma during the first months on combination antiretroviral therapy. AIDS. 2013;27:635–43. 9. Feller L, Anagnostopoulos C, Wood NH, Bouckaert M, Raubenheimer EJ, Lemmer J. Human immunodeficiency virus-associated Kaposi sarcoma as an immune reconstitution inflammatory syndrome: a literature review and case report. J Periodontol. 2008;79:362–8. 10. Bower M, Nelson M, Young AM, Thirlwell C, Newsom-Davis T, Mandalia S, et al. Immune reconstitution inflammatory syndrome associated with Kaposi’s sarcoma. J Clin Oncol. 2005;23:5224–8.
Conflict of interests
Gemma Melé-Ninot a,∗ , Joaquim Sola-Ortigosa a , Maribel Iglesias-Sancho a , Jordi Delás-Amat b
The authors report no conflict of interest in drafting the manuscript. References 1. Letang E, Lewis JJ, Bower M, Mosam A, Borok M, Campbell TB, et al. Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma: higher incidence and mortality in Africa than in the UK. AIDS. 2013;27: 1603–13.
Gastroparesis: An under-recognized complication after atrial fibrillation catheter ablation procedure夽 Gastroparesia: una complicación poco reconocida de la ablación percutánea de la fibrilación auricular Dear Editor, Percutaneous ablation of atrial fibrillation (AF) is an increasingly common treatment in daily clinical practice. In a recent European study incidence of complications secondary to catheter ablation of atrial fibrillation was 7.7%,1 being cardiovascular complications (mainly pericarditis) the most frequently reported. Among gastrointestinal complications, only one case of esophageal ulcer was reported. However, some cases of gastroparesis have been exceptionally described in the medical literature and its approach has not been established. We report 2 cases of gastroparesis after percutaneous ablation of AF. Both patients had symptomatic AF and refractory to antiarrhythmic therapy. Both of them underwent percutaneous ablation
夽 Please cite this article as: Calvo N, García de Yébenes-Castro M, Arguedas H, García-Bolao I. Gastroparesia: una complicación poco reconocida de la ablación percutánea de la fibrilación auricular. Med Clin (Barc). 2015;145:552–553.
a
Servicio de Dermatología, Hospital Universitari Sagrat Cor, Barcelona, Spain b Servicio de Medicina Interna, Hospital Universitari Sagrat Cor, Barcelona, Spain ∗ Corresponding author. E-mail address: [email protected] (G. Melé-Ninot).
of AF consisting of the circumferential isolation of pulmonary veins using non-fluoroscopic electroanatomic mapping system. Radiofrequency was used in both cases as an energy source, with an irrigated catheter with a temperature up to 40 ◦ C and a maximum power of 35 W. The procedure was performed without any complications and the patients were discharged after 24 h. A few days later the patients came to our center with symptoms of dyspnea, feeling of gastric fullness and epigastric pain. They underwent a CT scan and the presence of gastro-esophageal fistula was ruled out, but the CT showed a significant gastric dilation with food remains. Patients underwent an endoscopic study, which revealed small superficial erosions in the esophagus, and a study of gastric emptying, which showed gastric hypomotility. Treatment was initiated with prokinetic agents, proton-pump inhibitors and NPO. The symptoms were subsiding and oral diet was reintroduced with good tolerance after 3 days. Patients remain asymptomatic more than 12 months after ablation. In this paper we describe a poorly defined extracardiac complication of catheter ablation of atrial fibrillation caused by vagus nerve injury. To date, only a few cases of gastroparesis have been reported after using radiofrequency during percutaneous ablation of AF.2 The vagus nerve runs down and borders both sides of esophagus and trachea. The vagus nerve joins the sympathetic fibers at the back of the left atrium, forming a nerve plexus. In most cases, this plexus is located behind the right inferior pulmonary vein.3 Caudally, the vagus nerve is divided into two branches responsible for the innervation of the upper part of the digestive tract, controlling gastric motility and pylorus.4 Because of