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Fluctuating Anaemia in Treated HIV Patients: Could be a PICA?
Thérapie 2013 Janvier-Février; 68 (1): 49–51 DOI: 10.2515/therapie/2013010
PHARMACOVIGILANCE
© 2013 Société Française de Pharmacologie et de Thérapeutique
Fluctuating Anaemia in Treated HIV Patients: Could be a PICA? Faiza Ajana1, Armelle Pasquet1, Marine Auffret2 and Sophie Gautier2 1 Service Universitaire des Maladies infectieuses et du Voyageur, Centre Hospitalier, Tourcoing, France 2 Centre régional de Pharmacovigilance, Centre Hospitalo-Universitaire, Lille, France Text received November 23rd, 2012; accepted December 3rd, 2012
Keywords: anemia; PICA; HIV patients
Abstract – HIV infected patients are frequently exposed to anaemia, due to antiretroviral agents and/or prophylactic treatment of opportunistic infections. Anemia due to PICA, unusually evoked in our western countries, could be a more frequent situation than imagined. We report two cases of fluctuating anemia with no HIV or iatrogenic origin, observed in two HIV infected women, 47 years old and 33 years old respectively, coming from Africa and treated with antiretroviral agents. The anemia was explained by a culturally sanctioned practice of kaolin ingestion, in the broader context of PICA and resolved after the withdrawal of kaolin ingestion. PICA, and in particular kaolin ingestion, must be investigated when HIV infected patients came from Africa and presented significative unexplained anemia.
Mots clés : anémie ; PICA ; patients HIV
Résumé – Anémie chez le patient traité pour un HIV : penser au PICA. Les patients suivis pour un VIH sont fréquemment concernés par la survenue d’anémies, souvent liées à la prise de leur traitement, antirétroviral ou prophylactique, et/ou aux infections opportunistes. L’anémie liée à un PICA, hypothèse peu évoquée dans nos pays occidentaux, pourrait être une situation clinique plus fréquente qu’on imagine. Nous rapportons deux observations d’anémie fluctuante sans explication liée à l’infection ou aux traitements reçus, chez deux patientes d’origine africaine suivies pour un VIH, traitées par antirétroviraux. L’anémie est apparue en relation avec l’ingestion, d’origine culturelle, de kaolin dans un contexte de PICA et s’est résolue à l’arrêt de cette pratique. Un PICA, et notamment l’ingestion de kaolin, doit recherchée chez les patients d’origine africaine suivis pour un VIH, traités par antirétroviraux pour lesquels on observe une anémie inexpliquée par les traitements ou l’infection.
Abbreviations: see end of article.
1. Introduction
2. Cases reports
Human immunodeficiency virus (HIV) infected patients (HIVP) are frequently exposed to anaemia. Iatrogenic causes are especially related to antiretroviral agents (ARVs) and/or prophylactic treatment of opportunistic infections (OI). Over the last decade, the use of less or no haematotoxic ARVs and the progress in management of HIVP lead to a dramatic decrease of the incidence of anaemia. We report two cases of persistent anaemia in ladies who have a good immunologic status and a long term HIV viral load (VL) control (<1.3 log units). No HIV or iatrogenic aetiology was found to explain the fluctuating anaemia, confirmed to be related to the iterative ingestion of kaolin, a habit known as PICA, characterized by a persistent appetite for non-nutritive substances.
2.1. First case This case is a 47 year old woman from Rwanda, where she worked as a legal assistant, arrived in 1998 in France as a refugee. HIV infection was diagnosed in the aftermath of general weakness. ARVs were rapidly initiated. From 1999 to 2005, several skin, liver and haematological side effects conduct to modify ARVs and OI prophylaxis treatments. After a lost follow-up from 2005 to 2009, the patient restarted ARVs which were rapidly effective with a good clinical tolerance. The improvement in the patient’s general health status and immunovirological response contrasted with a chronic
Article publié par EDP Sciences
50
Ajana et al.
Treatment
Prezista/Norvir ®
Kaletra®
Atripla®
Prezista®: darunavir; Norvir®: ritonavir; Kaletra®: lopinavir, ritonavir; Atripla®: emtricitabine+tenofovir disoproxil+efavirenz
Atripla®: emtricitabine+tenofovir disoproxil+efavirenz
Fig. 1. Haemoglobin level in patient 1 in g/dL during and after kaolin consumption.
Fig. 2. Haemoglobin level in patient 2 in g/dL during and after kaolin consumption.
fluctuation of her haemoglobin levels between 8 and 13 g/dL (figure 1). Oral and parenteral iron supplementations were partially effective. No obvious cause of this chronic anaemia (bleeding, sepsis, haemoglobinopathy, iatrogenic, etc.) was found. More detailed patient interview with a focus on potential self-medication revealed the daily, compulsive consumption of kaolin clay paste bought in African products shops. The patient was ashamed to admit to kaolin ingestion and said that she was addicted to eating the substance. She was aware of the need to stop consuming kaolin since her teenage daughter had shrieked with horror when she surprised her mother eating the clay. The anaemia has since improved very slowly but relapses when the patient yields to her compulsion and resumes kaolin consumption from time to time. A long term psychological care is still ongoing.
rette smoking do. She further admitted that she was aware of the harmful effects of kaolin (especially during pregnancy) but was unable to give up. Psychological care is still ongoing.
2.2. Second case This case is a 33 year old lady from the Republic of Cameroon living in France since 2005. She is working as a care assistant in a retirement home. HIV diagnosis was confirmed in january 2011 after her test request. She subsequently agreed to participate in a double-blind, comparative trial of fixed-dose, three-component ARV treatments (dolutegravir+abacavir+epivir in the same tablet versus Atripla® (emtricitabine+tenofovir disoproxil+efavirenz)). The ARVs are effective and well tolerated but fluctuating, iron-deficiency anaemia is observed (figure 2). Aetiological screening ruled out iatrogenic or organic causes. The patient give a history of recent compulsive habit of ingesting white stones of kaolin. She used to buying stones in an African products shop for €3.50 each and consumes 6 to 8 stones per day (i.e. about one stone an hour). She says that kaolin gives her much the same sense of wellbeing as ciga-
© Société Française de Pharmacologie et de Thérapeutique
3. Discussion Kaolin, the main component of clay, is an aluminium silicate used in western societies as an antacid and as a treatment for digestive function disorders. The substances contained in kaolin may be associated with a decrease in the absorption of certain drugs, especially when used at high doses or for prolonged periods, and with the occurrence of iron-deficiency anaemia. As a negatively-charged adsorbent, kaolin binds cations (such as Fe2+ and Fe3+ ions) in the digestive tract and thus contributes to their poor absorption.[1] Iron-deficiency anaemia has been described in the broader context of pica eating disorders, i.e. the long-term consumption of non-nutritive substances (earth, roots, paper, soap, metals, etc.).[2] Although scientific data on the consequences of the consumption of large amounts of earthy or soil-like substances (also referred to as geophagy) are scarce, many internet forums, especially those for African communities, discuss the problems of pica and geophagy. It appears that kaolin use is very widespread in African women and in pregnant women in particular.[3] The problem of anaemia is widely mentioned and physicians in African countries have warned extensively of the risks of anaemia in the mother and the unborn child. A 2010 study on a population of 2 368 pregnant women in Zanzibar showed an association between PICA and anaemia, with a clear correlation between geophagy (5.3% of the women surveyed) and the severity of anaemia.[4] The kaolin clay can also contain micro-organisms and, most worryingly, parasitic intestinal worms which can aggravate the anaemia.[5]
Thérapie 2013 Janvier-Février; 68 (1)
51
PICA and anemia in HIV patients
Kaolin consumption is probably a true addiction because the women felt unwell when they stopped eating the substance. Our two case reports emphasize the temporary, compulsive ingestion evidenced by the fluctuating haemoglobin level. This addiction did not appear to perturb the family life or socioprofessional activities. The exact indications for initiating this type of consumption are not clear.[3] In addition to use as an antacid with wound-healing and antiseptic properties, kaolin supposedly also provides nutritional benefits by supplying macro- and micronutrients. Some women also mention that altered taste during pregnancy prompts them to consume kaolin. In fact, it appears that this consumption is not based on a precise set of indications and is mainly a culturally sanctioned practice. Since weight gain while on ARVs was a concern for both our patients, one can suppose that weight control was another reason for kaolin consumption.
4. Conclusion It is noteworthy that despite the presence of this PICA syndrome, the two patients have a stable clinical status and maintain their virological response to ARVs, suggesting the absence of a significant interaction between the treatment and the kaolin ingestion. This interaction can nonetheless legitimately be suspected given the kaolin’s adsorbent properties and considering that HIVP are advised not to take other medications such as antacids, vitamins, caloric supplements, etc. at the same time as their ARVs to precisely avoid their poor absorption. Finally, kaolin ingestion, or more broadly PICA, can induce, aggravate or maintain unexplained anaemia in HIV-infected patients treated with ARVs, apparently without interfering with ARVs efficacy. Pica syndrome is certainly poorly known and identified in western societies.[6] Establishing the true nature and frequency of this
© Société Française de Pharmacologie et de Thérapeutique
little-known condition may help to avoid expensive aetiological screening and to give support to these unsuspected patients with their compulsive behaviour. Conflicts of interests. None. Abbreviations. ARVs: antiretroviral agents; HIV: human immunodeficiency virus; HIVP: HIV infected patients; OI: opportunistic infections; VL: viral load.
References 1.
Khan Y, Tisman G. Pica in iron deficiency: a case-series. J Med Case reports 2010; 4: 86-8
2.
Crosby WH. Pica. JAMA 1976; 235: 2765
3.
Njiru H, Elchalal U, Paltiel O. Geophagy during pregnancy in Africa: a literature review. Obstet Gynecol Surv 2011; 66: 452-9
4.
Kawai K, Saathoff E, Antelman G, et al. Geophagy (soil-eating) in relation to anemia and helminth infection among HIV-infected pregnant women in Tanzania. Am J Trop Med Hyg 2009; 80: 36-43
5.
Young Sl, Khalfan SS, Farag TH, et al. Association of pica with anemia and gastrointestinal distress among pregnant women in Zanzibar, Tanzania. Am J Trop Med Hyg 2010; 83: 144-51
6.
Kettaneh A, Eclade V, Fain O, et al. Pica and food craving in patients with iron-deficiency anemia: a case-control study in France. Am J Med 2005; 118: 185-8
Correspondence and offprints: Sophie Gautier, Centre régional de Pharmacovigilance, 1 place de Verdun, 59045 Lille Cedex, France. E-mail: [email protected] Faiza Ajana, Service des Maladies infectieuses, Centre Hospitalier, 155 rue du Président Coty, 59200 Tourcoing, France. E-mail: [email protected]
Thérapie 2012 Janvier-Février; 68 (1)
PHARMACOVIGILANCE
© 2013 Société Française de Pharmacologie et de Thérapeutique
Fluctuating Anaemia in Treated HIV Patients: Could be a PICA? Faiza Ajana1, Armelle Pasquet1, Marine Auffret2 and Sophie Gautier2 1 Service Universitaire des Maladies infectieuses et du Voyageur, Centre Hospitalier, Tourcoing, France 2 Centre régional de Pharmacovigilance, Centre Hospitalo-Universitaire, Lille, France Text received November 23rd, 2012; accepted December 3rd, 2012
Keywords: anemia; PICA; HIV patients
Abstract – HIV infected patients are frequently exposed to anaemia, due to antiretroviral agents and/or prophylactic treatment of opportunistic infections. Anemia due to PICA, unusually evoked in our western countries, could be a more frequent situation than imagined. We report two cases of fluctuating anemia with no HIV or iatrogenic origin, observed in two HIV infected women, 47 years old and 33 years old respectively, coming from Africa and treated with antiretroviral agents. The anemia was explained by a culturally sanctioned practice of kaolin ingestion, in the broader context of PICA and resolved after the withdrawal of kaolin ingestion. PICA, and in particular kaolin ingestion, must be investigated when HIV infected patients came from Africa and presented significative unexplained anemia.
Mots clés : anémie ; PICA ; patients HIV
Résumé – Anémie chez le patient traité pour un HIV : penser au PICA. Les patients suivis pour un VIH sont fréquemment concernés par la survenue d’anémies, souvent liées à la prise de leur traitement, antirétroviral ou prophylactique, et/ou aux infections opportunistes. L’anémie liée à un PICA, hypothèse peu évoquée dans nos pays occidentaux, pourrait être une situation clinique plus fréquente qu’on imagine. Nous rapportons deux observations d’anémie fluctuante sans explication liée à l’infection ou aux traitements reçus, chez deux patientes d’origine africaine suivies pour un VIH, traitées par antirétroviraux. L’anémie est apparue en relation avec l’ingestion, d’origine culturelle, de kaolin dans un contexte de PICA et s’est résolue à l’arrêt de cette pratique. Un PICA, et notamment l’ingestion de kaolin, doit recherchée chez les patients d’origine africaine suivis pour un VIH, traités par antirétroviraux pour lesquels on observe une anémie inexpliquée par les traitements ou l’infection.
Abbreviations: see end of article.
1. Introduction
2. Cases reports
Human immunodeficiency virus (HIV) infected patients (HIVP) are frequently exposed to anaemia. Iatrogenic causes are especially related to antiretroviral agents (ARVs) and/or prophylactic treatment of opportunistic infections (OI). Over the last decade, the use of less or no haematotoxic ARVs and the progress in management of HIVP lead to a dramatic decrease of the incidence of anaemia. We report two cases of persistent anaemia in ladies who have a good immunologic status and a long term HIV viral load (VL) control (<1.3 log units). No HIV or iatrogenic aetiology was found to explain the fluctuating anaemia, confirmed to be related to the iterative ingestion of kaolin, a habit known as PICA, characterized by a persistent appetite for non-nutritive substances.
2.1. First case This case is a 47 year old woman from Rwanda, where she worked as a legal assistant, arrived in 1998 in France as a refugee. HIV infection was diagnosed in the aftermath of general weakness. ARVs were rapidly initiated. From 1999 to 2005, several skin, liver and haematological side effects conduct to modify ARVs and OI prophylaxis treatments. After a lost follow-up from 2005 to 2009, the patient restarted ARVs which were rapidly effective with a good clinical tolerance. The improvement in the patient’s general health status and immunovirological response contrasted with a chronic
Article publié par EDP Sciences
50
Ajana et al.
Treatment
Prezista/Norvir ®
Kaletra®
Atripla®
Prezista®: darunavir; Norvir®: ritonavir; Kaletra®: lopinavir, ritonavir; Atripla®: emtricitabine+tenofovir disoproxil+efavirenz
Atripla®: emtricitabine+tenofovir disoproxil+efavirenz
Fig. 1. Haemoglobin level in patient 1 in g/dL during and after kaolin consumption.
Fig. 2. Haemoglobin level in patient 2 in g/dL during and after kaolin consumption.
fluctuation of her haemoglobin levels between 8 and 13 g/dL (figure 1). Oral and parenteral iron supplementations were partially effective. No obvious cause of this chronic anaemia (bleeding, sepsis, haemoglobinopathy, iatrogenic, etc.) was found. More detailed patient interview with a focus on potential self-medication revealed the daily, compulsive consumption of kaolin clay paste bought in African products shops. The patient was ashamed to admit to kaolin ingestion and said that she was addicted to eating the substance. She was aware of the need to stop consuming kaolin since her teenage daughter had shrieked with horror when she surprised her mother eating the clay. The anaemia has since improved very slowly but relapses when the patient yields to her compulsion and resumes kaolin consumption from time to time. A long term psychological care is still ongoing.
rette smoking do. She further admitted that she was aware of the harmful effects of kaolin (especially during pregnancy) but was unable to give up. Psychological care is still ongoing.
2.2. Second case This case is a 33 year old lady from the Republic of Cameroon living in France since 2005. She is working as a care assistant in a retirement home. HIV diagnosis was confirmed in january 2011 after her test request. She subsequently agreed to participate in a double-blind, comparative trial of fixed-dose, three-component ARV treatments (dolutegravir+abacavir+epivir in the same tablet versus Atripla® (emtricitabine+tenofovir disoproxil+efavirenz)). The ARVs are effective and well tolerated but fluctuating, iron-deficiency anaemia is observed (figure 2). Aetiological screening ruled out iatrogenic or organic causes. The patient give a history of recent compulsive habit of ingesting white stones of kaolin. She used to buying stones in an African products shop for €3.50 each and consumes 6 to 8 stones per day (i.e. about one stone an hour). She says that kaolin gives her much the same sense of wellbeing as ciga-
© Société Française de Pharmacologie et de Thérapeutique
3. Discussion Kaolin, the main component of clay, is an aluminium silicate used in western societies as an antacid and as a treatment for digestive function disorders. The substances contained in kaolin may be associated with a decrease in the absorption of certain drugs, especially when used at high doses or for prolonged periods, and with the occurrence of iron-deficiency anaemia. As a negatively-charged adsorbent, kaolin binds cations (such as Fe2+ and Fe3+ ions) in the digestive tract and thus contributes to their poor absorption.[1] Iron-deficiency anaemia has been described in the broader context of pica eating disorders, i.e. the long-term consumption of non-nutritive substances (earth, roots, paper, soap, metals, etc.).[2] Although scientific data on the consequences of the consumption of large amounts of earthy or soil-like substances (also referred to as geophagy) are scarce, many internet forums, especially those for African communities, discuss the problems of pica and geophagy. It appears that kaolin use is very widespread in African women and in pregnant women in particular.[3] The problem of anaemia is widely mentioned and physicians in African countries have warned extensively of the risks of anaemia in the mother and the unborn child. A 2010 study on a population of 2 368 pregnant women in Zanzibar showed an association between PICA and anaemia, with a clear correlation between geophagy (5.3% of the women surveyed) and the severity of anaemia.[4] The kaolin clay can also contain micro-organisms and, most worryingly, parasitic intestinal worms which can aggravate the anaemia.[5]
Thérapie 2013 Janvier-Février; 68 (1)
51
PICA and anemia in HIV patients
Kaolin consumption is probably a true addiction because the women felt unwell when they stopped eating the substance. Our two case reports emphasize the temporary, compulsive ingestion evidenced by the fluctuating haemoglobin level. This addiction did not appear to perturb the family life or socioprofessional activities. The exact indications for initiating this type of consumption are not clear.[3] In addition to use as an antacid with wound-healing and antiseptic properties, kaolin supposedly also provides nutritional benefits by supplying macro- and micronutrients. Some women also mention that altered taste during pregnancy prompts them to consume kaolin. In fact, it appears that this consumption is not based on a precise set of indications and is mainly a culturally sanctioned practice. Since weight gain while on ARVs was a concern for both our patients, one can suppose that weight control was another reason for kaolin consumption.
4. Conclusion It is noteworthy that despite the presence of this PICA syndrome, the two patients have a stable clinical status and maintain their virological response to ARVs, suggesting the absence of a significant interaction between the treatment and the kaolin ingestion. This interaction can nonetheless legitimately be suspected given the kaolin’s adsorbent properties and considering that HIVP are advised not to take other medications such as antacids, vitamins, caloric supplements, etc. at the same time as their ARVs to precisely avoid their poor absorption. Finally, kaolin ingestion, or more broadly PICA, can induce, aggravate or maintain unexplained anaemia in HIV-infected patients treated with ARVs, apparently without interfering with ARVs efficacy. Pica syndrome is certainly poorly known and identified in western societies.[6] Establishing the true nature and frequency of this
© Société Française de Pharmacologie et de Thérapeutique
little-known condition may help to avoid expensive aetiological screening and to give support to these unsuspected patients with their compulsive behaviour. Conflicts of interests. None. Abbreviations. ARVs: antiretroviral agents; HIV: human immunodeficiency virus; HIVP: HIV infected patients; OI: opportunistic infections; VL: viral load.
References 1.
Khan Y, Tisman G. Pica in iron deficiency: a case-series. J Med Case reports 2010; 4: 86-8
2.
Crosby WH. Pica. JAMA 1976; 235: 2765
3.
Njiru H, Elchalal U, Paltiel O. Geophagy during pregnancy in Africa: a literature review. Obstet Gynecol Surv 2011; 66: 452-9
4.
Kawai K, Saathoff E, Antelman G, et al. Geophagy (soil-eating) in relation to anemia and helminth infection among HIV-infected pregnant women in Tanzania. Am J Trop Med Hyg 2009; 80: 36-43
5.
Young Sl, Khalfan SS, Farag TH, et al. Association of pica with anemia and gastrointestinal distress among pregnant women in Zanzibar, Tanzania. Am J Trop Med Hyg 2010; 83: 144-51
6.
Kettaneh A, Eclade V, Fain O, et al. Pica and food craving in patients with iron-deficiency anemia: a case-control study in France. Am J Med 2005; 118: 185-8
Correspondence and offprints: Sophie Gautier, Centre régional de Pharmacovigilance, 1 place de Verdun, 59045 Lille Cedex, France. E-mail: [email protected] Faiza Ajana, Service des Maladies infectieuses, Centre Hospitalier, 155 rue du Président Coty, 59200 Tourcoing, France. E-mail: [email protected]
Thérapie 2012 Janvier-Février; 68 (1)