- Email: [email protected]
The importance of laboratory re-evaluation in cases of suspected child abuse – A case report
Accepted Manuscript Case Report The importance of laboratory re-evaluation in cases of suspected child abuse – A case report L. Woydt, C. König, M.K. Bernhard, P. Nickel, J. Dreßler, B. Ondruschka PII: DOI: Reference:
S1344-6223(17)30195-5 http://dx.doi.org/10.1016/j.legalmed.2017.07.007 LEGMED 1431
To appear in:
Legal Medicine
Received Date: Accepted Date:
19 May 2017 24 July 2017
Please cite this article as: Woydt, L., König, C., Bernhard, M.K., Nickel, P., Dreßler, J., Ondruschka, B., The importance of laboratory re-evaluation in cases of suspected child abuse – A case report, Legal Medicine (2017), doi: http://dx.doi.org/10.1016/j.legalmed.2017.07.007
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
The importance of laboratory re-evaluation in cases of suspected child abuse – A case report Woydt L1, König C1, Bernhard MK2, Nickel P2, Dreßler J,1 Ondruschka B1 1
Institute of Legal Medicine, Medical Faculty, University of Leipzig
2
Hospital for Children and Adolescents, Centre for Paediatric Research, University of Leipzig
Corresponding author:
Dr. med. Benjamin Ondruschka University of Leipzig, Medical Faculty Institute of Legal Medicine Johannisallee 28 D-04103 Leipzig Email: [email protected]
The importance of laboratory re-evaluation in cases of suspected child abuse – A case report Abstract In order to accurately diagnose child abuse or neglect, a physician needs to be familiar with diseases and medical conditions that can simulate maltreatment. Unrecognized cases of abuse may lead to insufficient child protection, whereas, on the other hand, over-diagnosis could be the cause of various problems for the family and their potentially accused members. Regarding child abuse, numerous cases of false diagnoses with undetected causes of bleeding are described in the scientific literature, but, specifically concerning leukemia in childhood, only very few case reports exist. Here, for the first time, we report a case of a 2-year-old boy who got hospitalized twice because of suspicious injuries and psychosocial conspicuities, in a family situation known for repeated endangerment of the child’s well-being. After his first hospitalization with injuries typical for child abuse, but without paraclinical abnormalities, medical inspections were arranged periodically. The child was hospitalized with signs of repeated child abuse again five months later. During second admission, an acute lymphoblastic leukemia was revealed by intermittent laboratory examination, ordered due to new bruises with changes in morphology, identifiable as petechial hemorrhages. This case elucidates the discussion of known cases of leukemia in childhood associated with suspected child abuse in order to provide an overview of possible diseases mimicking maltreatment. To arrange necessary supportive examinations, a skillful interaction between pediatrician and forensic pathologist is crucial in the differentiation between accidental and non-accidental injury.
Keywords: acute lymphoblastic leukemia – misdiagnosed child abuse – non-accidental injury – petechial hemorrhage
Introduction Bruising is the most frequent sign of child abuse 1,2 during childhood, but bruises are also a symptom of a wide variety of diseases such as leukemia. 3,4 With an annual incidence of 45 in 1,000,000 children less than 16 years of age, leukemias are a rather rare disease, but nevertheless the most frequent type of malignoma in childhood.5 In 2015, 452 cases of acute lymphoblastic leukemia (ALL) were diagnosed in children below the age of 15 in Germany. 6 However, the record ‘child abuse’ had been registered seven times more frequently than ALL for the same year7, and assumingly a considerably high estimated number of unreported or misinterpreted cases. The peak incidence of ALL in children occurs between the ages of three and five.8 Children who are most vulnerable to child abuse are younger than six years, with the highest incidence among children under the age of one9, affecting nearly the same age group as ALL. Bruises are considered normal for children, though there are some characteristics which help to discriminate between accidental and non-accidental injuries, especially bleedings in multiple areas and in unusual regions, bruising in various stages depending on age, and patterned injuries.3,4 Apart from this, other lesions such as fractures, scars, or burns can support the suspicion of child abuse, as well as a history that doesn’t fully explain the nature of those findings.10 Therefore, the plausibility of circumstances leading to the injury, often described and presented by the parents, should always be reassessed. ALL in childhood can show varying symptoms that complicate the diagnostic workup. Intensive bruising as well as severe hematological disorders10,11, and even patients without any cutaneous signs are known Here we report the case of a 2-year-old boy who was brought to hospital twice at an interval of five months due to bruises of unknown origin. During the second admission an ALL was diagnosed.
Case report First hospitalization A boy of 2 years and 4 months of age was admitted to hospital by child protective services due to multiple bruises of unknown origin. He had already been known previously for having a Kartagener syndrome presenting with an inverse situs and several airway infections, but nothing about a suspected child abuse was found in the medical documentation. During admission a solid general state and eutrophic nutritional condition were assessed, with a height of 85.5 cm (Percentile 12), a weight of 11.3 kg (Percentile 16) and a BMI of 15.5
kg/m² (Percentile 33). A balanitis was reported in the anamnesis, which according to the mother’s statement had been the consequence of a forced retraction of the prepuce. The boy’s skin showed several brownish-yellow bruises. Internal injuries were excluded by ultrasound examination. A forensic consultative examination was required to rule out the suspicion of child abuse. During this examination, three bruises in slightly different intensity was found on the boy’s forehead, as well as two bruises on the middle and upper left cheek, partly not on top of bony structures (see Figure 1). Furthermore, there were scabbed excoriations on his lower abdomen (see Figure 2) and healing rhagades on the root of his penis. From a forensic point of view, the excoriations on the abdomen had been the result of a forced tangential violence, perhaps following a manipulation on the boy’s trousers. The rhagades could best be explained by a forceful traction of the penis. However, a retraction of the prepuce tends to cause dermal abrasions, even a disrupture of the frenulum, but not injuries at the root of the penis. Therefore, the findings on the left cheek, lower abdomen and penis were classified as nonaccidental injuries. After the mother had been informed about the examination results, she stated that her son was very ‘clumsy’ and had bounced against a doorframe – an explanation which could not have plausibly led to those two-sided injuries on his head; according to her, the injury of the lower abdomen appeared to have been the consequence of an exertion of pressure in order to stimulate his urination. To rule out hematological and coagulation disorders as internal reasons for bruising, an extensive blood investigation was performed. The laboratory results showed no pathological findings (see Table 1). Due to the suspected injury patterns and their multiplicity, a child endangerment had been affirmed after the forensic investigation. The partially ambivalent behaviour of the mother supported her hazard potential for the boy. He was discharged from hospital with child protective services ensuring that the child would undergo periodic medical inspections for follow-up.
Second hospitalization Five months later the boy was sent to the hospital by his resident pediatrician, because of a progressive swelling of the soft tissues over the left eye with a surrounding bruise found during follow-up examination.
During this admission to hospital, a steady general and nutritive condition could be assessed again. The boy and his clothes were soiled and a general paleness was noticed. Another forensic examination was performed because of the soft tissue lesions around his left eye. There, slightly streaky bruising with small petechial hemorrhages at the skin of the eye lid as well as the surrounding skin, yet without any bulbar or conjunctival involvement, attracted attention (see Figure 3). Additionally, two older bruises were found at the temples. On the back, a bruise presenting with numerous single punctate bleedings was visible (see Figure 4). The mother stated that the boy had rubbed his eyes the day before and had injured himself. She also recalled that a vase had fallen onto his back. From a forensic view, blunt force trauma through impact or slap in the face was suspected, but the mother’s version couldn’t be refuted. The impact of a vase could explain the location and intensity of the documented bruise on the boy’s back, yet the morphology with punctate bleedings remained uncharacteristic of blunt force acting on a healthy child’s body. Other non-accidental trauma mechanisms like throws or kicks could not be excluded, too. Based on these petechial hemorrhages, laboratory diagnostics were requested once more. The results showed severe abnormalities concerning the hematopoietic system, in particular an existing anemia, thrombocytopenia and leukocytosis with abnormally high amount of blasts (see Table 1). After immunological characterization of those blasts via bone marrow puncture, a so-called common-ALL could be diagnosed. Following this, a therapy scheme using the AIEOP-BFM (Italian Association of Pediatric Hematology and Oncology / Berlin-FrankfurtMünster) ALL 2009 guidelines was initiated, which led to complete remission of the disease without causing severe complications. During chemotherapy the family had been under intensive psychosocial care. Due to distinctive deficiency states with lack of support by the parent and signs of a general developmental and linguistic delay in her child, as well as signs of actual substance abuse by the mother and, lastly, the boy’s preexisting disease, his accommodation in a foster family had been ordered by child protective services a few months after the second admission. Since that, the boy has never again been presented with suspected injury to his body, neither to his pediatrician nor the hospital, and has been in good general condition. He has received periodic medical examinations to evaluate his pulmonal state due to Kartagener syndrome. His lung function has been sufficiently good and there have been no relevant airway complications like bronchiectasis in the recent past. The ALL is still in remission for more than two years at this point in time.
Discussion With 33%, leukemias are the most common malignomas in childhood 5,8, whereby 75-80% of them are classified as ALL. Resulting from the intensity of bone marrow infiltration by leukemic cells and the extramedullary spreading of the malady, the symptoms can vary strongly. The duration of symptoms may last days, weeks, even several months. The severity of the disease reaches from more or less asymptomatic patients with only spontaneous bruising to heavily invalid children suffering from infections, fatigue and bleeding due to the changes in blood count. Further symptoms could be hepatosplenomegaly, enlarged lymph nodes, or even meningeal signs, in cases where the central nervous system has been affected. 5 The thrombocytes are usually low, resulting in spontaneous hemorrhage with petechial nature in children with less than 20-30 Gpt/l. Although coagulopathies in consequence of hyperleukocytosis are more common in children with acute myeloid leukemia (AML), they can occur in both forms of leukemia, ALL and AML. Long-term remission rates in adequatly treated children with ALL amount to approx. 80%.5 Only four cases of acute leukemia mimicking non-accidental injury have been reported before, three of them were diagnosed as ALL. Only one of those ALL cases was diagnosed during lifetime. To the best of our knowledge, no case report exists that comprises a confirmed medical history of child abuse and ALL onset being discovered in wake of the follow-up investigation. McClain et al.11 have reported the postmortem case of a 2-year-old girl who had been found unresponsive at home and later died in spite of intensive medical treatment. She showed several bruises of different colors in multiple suspicious locations, petechial hemorrhages, and also there had been an anonymous report of child abuse one month before she died. By autopsy, an unrecognised ALL was diagnosed, which might have been the reason for the notifiable bruising leading to the anonymous report, but there had not been any medical examination or laboratory control during lifetime. However, in a case described by Tattoli et al.12, a boy of 4 months had died with suspicion of neglect and in a state of severe malnutrition and dehydration, but without any cutaneous findings that could indicate physical child abuse. Here, autopsy revealed an ALL as cause of death. Nadjem et al. reported the case of a 4-year-old girl with petechial bruising in multiple areas susceptive to abuse, whereby the diagnosis ALL could readily be made after admission using laboratory investigation. 10 And a case of AML in a 3 year-old girl had been mistaken for child abuse with symptoms of ecchymotic lesions and weight loss with laboratory proven pancytopenia. 13
So far this case is an exception, with the phenomenon of there being widespread laboratory diagnosis during first hospitalization, ruling out relevant bleeding or hematological disorders, but with severe abnormalities being examined five months later, leading to the diagnosis ALL. In both instances, suspected injuries with a deficient medical history presumed possible cases of child abuse. The petechial nature of the bruises during the second admission, which can always be a sign of thrombocytopenia, led to repeated laboratory investigations. 14 Therefore, even in known cases of child abuse and follow-up, a thorough reevaluation is essential in every examination, as not only congenital but also acquired disorders can be the cause of bruising, which may individually lead to repeated laboratory testing. On the contrary, children with known coagulopathies can get abused as well, which leads to difficulties in differentiation between accidental and non-accidental injuries.15,16 Therefore, we consider a functional interdisciplinary approach between experienced pediatricians and forensic pathologists with special expertise in clinical forensic medicine as essential. Otherwise, findings that reinforce the suspicion of physical abuse, especially at the beginning of the examination, may lead to premature judgement, avoiding consequent differential diagnosing. In this report, we concentrate on cutaneous findings mimicking child abuse, though there are many other medical conditions which can lead to mistakenly suspected abuse. 14 Because the problem of mistaken child abuse is very sensitive, there have been some publications analyzing cohorts of children with suspected maltreatment and illustrating the medical conditions that were responsible for the false accusation. 1,2,14-17 The most frequent congenital bleeding disorders potentially mimicking child abuse are hemophilia and Von Willebrand disease (vWD). 2 Other medical conditions that frequently appear in different reports are Mongolian spots14-16, hemangioma14-16 and idiopathic thrombocytopenic purpura13-15. In the most comprehensive study so far 15, 2890 children with suspected abuse, from which 137 had at least one abuse-mimicking condition, have prospectively been evaluated. No less than 31 different causes for cutaneous findings were listed, but not a single case was associated with leukemia. Further possible causes are even more infrequent and only appear in few case reports, such as Schönlein-Henoch purpura15,18 or Ehlers-Danlos syndrome16,19. The procedure of hematologic evaluation in suspected child abuse is inconsistently performed in different clinics.1 A pediatrician should implement a basic laboratory examination, and if there are no pathological findings, but the suspicion of bleeding disorder is still present, he would have to consult a pediatric hematologist. In a recent study20, an initial testing panel for bruising
has
been recommended,
containing prothrombin time,
activated partial
thromboplastin time, vWF antigen, vWF activity (Ristocetin cofactor), factor-VIII level, factor-IX level and a complete blood count (CBC) with platelet count. Other authors21 recommend additional testing of thrombin time, factor-XIII level and PFA-100, which might be tested in a second panel. With these parameters, an adequate quantity of potential medical bleeding disorders, including the aforementioned most frequent ones, could either be diagnosed or ruled out. The petechial nature of the bruising was an important suggestion for repeated blood measurements, as this is indicative for hematological diseases. 10 Repeated CBC testing would surely reveal the ALL during second admission, so the guideline-based medical treatment could immediately be started and a rare but, if left untreated, lifethreatening disease could be spotted in good time.
Conclusion ALL in childhood is a rare disease that needs to be diagnosed as fast as possible to allow lifesaving medical treatment. Bruising due to this malignant illness can be mistaken for child maltreatment, delaying therapy and causing legal problems for parents and guardians as well as the child.
It is crucial to have effective communication and interaction between
pediatricians and forensic pathologists to differentiate between accidental and non-accidental injuries and to arrange the necessary supportive examinations, including an initial laboratory blood test to exclude frequent bleeding disorders, especially if punctate bleedings are visible. Because children known for possible physical abuse can acquire bleeding disorders, and patients with acquainted bleeding disorders can be the targets of such abuse, too, it is of the utmost importance after hospital admission to reevaluate every child exposed to suspected child abuse and to avoid ‘tunnel vision’ in the on-going assessment of those young patients previously diagnosed with abusive type injuries.
Compliance with Ethical Standards. Ethics: This article does not contain any studies with human or animal participants performed by any of the authors. Conflicts of Interest: The authors declare that they have no conflict of interest. Acknowledgments: We want to thank Mr. Jakob Anselm for his careful support in language editing.
References 1 Paroskie A, Carpenter SL, Lowen DE, Anderst J, DeBaun MR, Sidonio RF Jr (2014) A two-center retrospective review of the hematologic evaluation and laboratory abnormalities in suspected victims of non-accidental injury. Child Abuse Negl 38:1794-1800 2 Jackson J, Carpenter S, Anderst C (2012) Challenges in the evaluation for possible abuse: presentations of congenital bleeding disorders in childhood. Child Abuse Negl 36:127-134 3 Mudd SS, Findlay JS (2004) The cutaneous manifestations and common mimickers of physical child abuse. J Pediatr Health Care 18:123-129 4 Kodner C, Wetherton A (2013) Diagnosis and management of physical abuse in children. Physician 88:669-675
Am Fam
5 Imbach P (2005) Acute lymphoblastic leukemia. In: Pediatric Oncology, Springer-Verlag Berlin Heidelberg, p. 11-28 6 Kaatsch P, Spix C (2015) German childhood cancer registry – annual report (1980-2014). Institute for Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg-University Mainz. 7 Bundesministerium des Inneren (2015), Polizeiliche Kriminalstatistik. https://www.bmi.bund.de/SharedDocs/Downloads/DE/Broschueren/2016/pks-2015.pdf?_blob= publicationFile (accessed 12.12.16) 8 Hunger SP, Mullighan CG (2015) Acute lymphoblastic leukemia in children. N Engl J Med 373:1541-1552 9 Department of Health & Human Services USA (2016). Child maltreatment 2014. https://www.acf.hhs.gov/sites/default/files/cb/cm2014.pdf (accessed 12.12.16) 10 Nadjem H, Sutor AH (1991) Hämatome bei akuter Leukose – Verdachtsdiagnose einer Kindesmißhandlung. Beitr Gerichtl Med 49:227-231 11 McClain JL, Clark MA, Sandusky GE (1990) Undiagnosed, untreated acute lymphoblastic leukemia presenting as suspected child abuse. J Forensic Sci 35:735-739 12 Tattoli L, Leonardi S, Carabellese S, Solarino B (2012) Acute lymphoblastic leukemia misdiagnosed as lethal child neglect. Rom J Leg Med 20:111-116 13 Scimeca PG, Cooper LB, Sahdev I (1996) Suspicion of child abuse complicating the diagnosis of bleeding disorders. Pediatr Hematol Oncol 13:179-182 14 Wheeler DM, Hobbs CJ (1988) Mistakes in diagnosing non-accidental injury: 10 years' experience. Br Med J 296:1233-1236
15 Schwartz KA, Metz J, Feldman K, Sidbury R, Lindberg DM, the ExSTRA Investigartors (2014) Cutaneous findings mistaken for physical abuse: present but not pervasive. Pediatr Dermatol 31:146155 16 Wardinsky TD, Vizcarrondo FE, Cruz BK (1995) The mistaken diagnosis of child abuse: A threeyear USAF Medical Center analysis and literature review. Mil Med 160:15-20 17 O’Hare AE, Eden OB (1984) Bleeding disorders and non-accidental injury. Arch Dis Child 59:860864 18 Brown J, Melinkovich P (1986) Schönlein-Henoch purpura misdiagnosed as suspected child abuse: a case report and literature review. JAMA 256:617-618 19 Castori M (2015) Ehlers–Danlos syndrome(s) mimicking child abuse: is there an impact on clinical practice? Am J Med Genet C 169:289-292 20 Anderst JD, Carpenter SL, Abshire TC, Section on Hematology/Oncology and Committee on Child Abuse and Neglect of the American Academy of Pediatrics (2013) Evaluation for bleeding disorders in suspected child abuse. Pediatrics 131:e1314-e1322 21 Minford AM, Richards EM (2010) Excluding medical and haematological conditions as a cause of bruising in suspected non-accidental injury. Arch Dis Child Educ Pract Ed 95:2-8
Figure legends
Fig. 1: Frontal photograph of the face with several notable bruises varying in intensity (taken during first admission to hospital).
Fig. 2: Picture of the lower abdomen with extensive excoriations and a surrounding bruising as well as healing rhagades around the root of the penis (taken during first admission).
Fig. 3: Lateral photograph of the left half of the face with slightly streaky appearance of the bruises and clearly visible petechial hemorrhages (taken during second admission to hospital).
Fig. 4: Picture of the left half of the bruised back with numerous single punctate bleedings (taken during second admission).
Tables Table 1. Laboratory findings during admission Hemoglobin (normal: 6.7-7.9 mmol/l) Hematocrit (normal: 0.34-0.4 l/l) Leucocytes (normal: 5-12 Gpt/l) Thrombocytes (normal: 140-360 Gpt/l) Retikulocytes (normal: 4.8-16.4/1000) Lymphocytes (normal: 13-55 %) Blasts (normal: negative) Atypical lymphocytes reactive (normal: negative) Granulocytes unsegmented (normal: 3-5 %) Granuloytes segmented (normal: 30-75 %) Anisocytosis
First admission 7.6 mmol/l
Second admission 4.8 mmol/l -
0.38 l/l
0.23 l/l -
6.4 Gpt/l
22.2 Gpt/l +
264 Gpt/l
28 Gpt/l 6.0/1000
52.3 %
76.0 % + 75.5 % + 6%+ 1.1 % 2.7 % ++
During the first investigation the following laboratory values were collected: Quick (98 %), aPTT (32.5 s), vWF antigen (77 %), Ristocetin cofactor activity (74 %), factor-VIII activity (91.4 %), factor-XIII activity (135 %), PFA collagen/ADP (105 s) and PFA collagen/epinephrine (138 s) to exclude a clotting disorder. All investigations resulted in normal ranges. The lymphomonocytic hemogram revealed an absolute neutropenia (0.56) during second admission. Pathological laboratory values are presented in bold print.
Highlights:
physicians needs to be familiar with medical conditions that can simulate maltreatment
interdisciplinary teamwork is necessary to match all investigation results with the present history
petechial nature of bruisings are important suggestions for hematological diseases
initial laboratory blood tests are necessary in context of non-accidental injuries
S1344-6223(17)30195-5 http://dx.doi.org/10.1016/j.legalmed.2017.07.007 LEGMED 1431
To appear in:
Legal Medicine
Received Date: Accepted Date:
19 May 2017 24 July 2017
Please cite this article as: Woydt, L., König, C., Bernhard, M.K., Nickel, P., Dreßler, J., Ondruschka, B., The importance of laboratory re-evaluation in cases of suspected child abuse – A case report, Legal Medicine (2017), doi: http://dx.doi.org/10.1016/j.legalmed.2017.07.007
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
The importance of laboratory re-evaluation in cases of suspected child abuse – A case report Woydt L1, König C1, Bernhard MK2, Nickel P2, Dreßler J,1 Ondruschka B1 1
Institute of Legal Medicine, Medical Faculty, University of Leipzig
2
Hospital for Children and Adolescents, Centre for Paediatric Research, University of Leipzig
Corresponding author:
Dr. med. Benjamin Ondruschka University of Leipzig, Medical Faculty Institute of Legal Medicine Johannisallee 28 D-04103 Leipzig Email: [email protected]
The importance of laboratory re-evaluation in cases of suspected child abuse – A case report Abstract In order to accurately diagnose child abuse or neglect, a physician needs to be familiar with diseases and medical conditions that can simulate maltreatment. Unrecognized cases of abuse may lead to insufficient child protection, whereas, on the other hand, over-diagnosis could be the cause of various problems for the family and their potentially accused members. Regarding child abuse, numerous cases of false diagnoses with undetected causes of bleeding are described in the scientific literature, but, specifically concerning leukemia in childhood, only very few case reports exist. Here, for the first time, we report a case of a 2-year-old boy who got hospitalized twice because of suspicious injuries and psychosocial conspicuities, in a family situation known for repeated endangerment of the child’s well-being. After his first hospitalization with injuries typical for child abuse, but without paraclinical abnormalities, medical inspections were arranged periodically. The child was hospitalized with signs of repeated child abuse again five months later. During second admission, an acute lymphoblastic leukemia was revealed by intermittent laboratory examination, ordered due to new bruises with changes in morphology, identifiable as petechial hemorrhages. This case elucidates the discussion of known cases of leukemia in childhood associated with suspected child abuse in order to provide an overview of possible diseases mimicking maltreatment. To arrange necessary supportive examinations, a skillful interaction between pediatrician and forensic pathologist is crucial in the differentiation between accidental and non-accidental injury.
Keywords: acute lymphoblastic leukemia – misdiagnosed child abuse – non-accidental injury – petechial hemorrhage
Introduction Bruising is the most frequent sign of child abuse 1,2 during childhood, but bruises are also a symptom of a wide variety of diseases such as leukemia. 3,4 With an annual incidence of 45 in 1,000,000 children less than 16 years of age, leukemias are a rather rare disease, but nevertheless the most frequent type of malignoma in childhood.5 In 2015, 452 cases of acute lymphoblastic leukemia (ALL) were diagnosed in children below the age of 15 in Germany. 6 However, the record ‘child abuse’ had been registered seven times more frequently than ALL for the same year7, and assumingly a considerably high estimated number of unreported or misinterpreted cases. The peak incidence of ALL in children occurs between the ages of three and five.8 Children who are most vulnerable to child abuse are younger than six years, with the highest incidence among children under the age of one9, affecting nearly the same age group as ALL. Bruises are considered normal for children, though there are some characteristics which help to discriminate between accidental and non-accidental injuries, especially bleedings in multiple areas and in unusual regions, bruising in various stages depending on age, and patterned injuries.3,4 Apart from this, other lesions such as fractures, scars, or burns can support the suspicion of child abuse, as well as a history that doesn’t fully explain the nature of those findings.10 Therefore, the plausibility of circumstances leading to the injury, often described and presented by the parents, should always be reassessed. ALL in childhood can show varying symptoms that complicate the diagnostic workup. Intensive bruising as well as severe hematological disorders10,11, and even patients without any cutaneous signs are known Here we report the case of a 2-year-old boy who was brought to hospital twice at an interval of five months due to bruises of unknown origin. During the second admission an ALL was diagnosed.
Case report First hospitalization A boy of 2 years and 4 months of age was admitted to hospital by child protective services due to multiple bruises of unknown origin. He had already been known previously for having a Kartagener syndrome presenting with an inverse situs and several airway infections, but nothing about a suspected child abuse was found in the medical documentation. During admission a solid general state and eutrophic nutritional condition were assessed, with a height of 85.5 cm (Percentile 12), a weight of 11.3 kg (Percentile 16) and a BMI of 15.5
kg/m² (Percentile 33). A balanitis was reported in the anamnesis, which according to the mother’s statement had been the consequence of a forced retraction of the prepuce. The boy’s skin showed several brownish-yellow bruises. Internal injuries were excluded by ultrasound examination. A forensic consultative examination was required to rule out the suspicion of child abuse. During this examination, three bruises in slightly different intensity was found on the boy’s forehead, as well as two bruises on the middle and upper left cheek, partly not on top of bony structures (see Figure 1). Furthermore, there were scabbed excoriations on his lower abdomen (see Figure 2) and healing rhagades on the root of his penis. From a forensic point of view, the excoriations on the abdomen had been the result of a forced tangential violence, perhaps following a manipulation on the boy’s trousers. The rhagades could best be explained by a forceful traction of the penis. However, a retraction of the prepuce tends to cause dermal abrasions, even a disrupture of the frenulum, but not injuries at the root of the penis. Therefore, the findings on the left cheek, lower abdomen and penis were classified as nonaccidental injuries. After the mother had been informed about the examination results, she stated that her son was very ‘clumsy’ and had bounced against a doorframe – an explanation which could not have plausibly led to those two-sided injuries on his head; according to her, the injury of the lower abdomen appeared to have been the consequence of an exertion of pressure in order to stimulate his urination. To rule out hematological and coagulation disorders as internal reasons for bruising, an extensive blood investigation was performed. The laboratory results showed no pathological findings (see Table 1). Due to the suspected injury patterns and their multiplicity, a child endangerment had been affirmed after the forensic investigation. The partially ambivalent behaviour of the mother supported her hazard potential for the boy. He was discharged from hospital with child protective services ensuring that the child would undergo periodic medical inspections for follow-up.
Second hospitalization Five months later the boy was sent to the hospital by his resident pediatrician, because of a progressive swelling of the soft tissues over the left eye with a surrounding bruise found during follow-up examination.
During this admission to hospital, a steady general and nutritive condition could be assessed again. The boy and his clothes were soiled and a general paleness was noticed. Another forensic examination was performed because of the soft tissue lesions around his left eye. There, slightly streaky bruising with small petechial hemorrhages at the skin of the eye lid as well as the surrounding skin, yet without any bulbar or conjunctival involvement, attracted attention (see Figure 3). Additionally, two older bruises were found at the temples. On the back, a bruise presenting with numerous single punctate bleedings was visible (see Figure 4). The mother stated that the boy had rubbed his eyes the day before and had injured himself. She also recalled that a vase had fallen onto his back. From a forensic view, blunt force trauma through impact or slap in the face was suspected, but the mother’s version couldn’t be refuted. The impact of a vase could explain the location and intensity of the documented bruise on the boy’s back, yet the morphology with punctate bleedings remained uncharacteristic of blunt force acting on a healthy child’s body. Other non-accidental trauma mechanisms like throws or kicks could not be excluded, too. Based on these petechial hemorrhages, laboratory diagnostics were requested once more. The results showed severe abnormalities concerning the hematopoietic system, in particular an existing anemia, thrombocytopenia and leukocytosis with abnormally high amount of blasts (see Table 1). After immunological characterization of those blasts via bone marrow puncture, a so-called common-ALL could be diagnosed. Following this, a therapy scheme using the AIEOP-BFM (Italian Association of Pediatric Hematology and Oncology / Berlin-FrankfurtMünster) ALL 2009 guidelines was initiated, which led to complete remission of the disease without causing severe complications. During chemotherapy the family had been under intensive psychosocial care. Due to distinctive deficiency states with lack of support by the parent and signs of a general developmental and linguistic delay in her child, as well as signs of actual substance abuse by the mother and, lastly, the boy’s preexisting disease, his accommodation in a foster family had been ordered by child protective services a few months after the second admission. Since that, the boy has never again been presented with suspected injury to his body, neither to his pediatrician nor the hospital, and has been in good general condition. He has received periodic medical examinations to evaluate his pulmonal state due to Kartagener syndrome. His lung function has been sufficiently good and there have been no relevant airway complications like bronchiectasis in the recent past. The ALL is still in remission for more than two years at this point in time.
Discussion With 33%, leukemias are the most common malignomas in childhood 5,8, whereby 75-80% of them are classified as ALL. Resulting from the intensity of bone marrow infiltration by leukemic cells and the extramedullary spreading of the malady, the symptoms can vary strongly. The duration of symptoms may last days, weeks, even several months. The severity of the disease reaches from more or less asymptomatic patients with only spontaneous bruising to heavily invalid children suffering from infections, fatigue and bleeding due to the changes in blood count. Further symptoms could be hepatosplenomegaly, enlarged lymph nodes, or even meningeal signs, in cases where the central nervous system has been affected. 5 The thrombocytes are usually low, resulting in spontaneous hemorrhage with petechial nature in children with less than 20-30 Gpt/l. Although coagulopathies in consequence of hyperleukocytosis are more common in children with acute myeloid leukemia (AML), they can occur in both forms of leukemia, ALL and AML. Long-term remission rates in adequatly treated children with ALL amount to approx. 80%.5 Only four cases of acute leukemia mimicking non-accidental injury have been reported before, three of them were diagnosed as ALL. Only one of those ALL cases was diagnosed during lifetime. To the best of our knowledge, no case report exists that comprises a confirmed medical history of child abuse and ALL onset being discovered in wake of the follow-up investigation. McClain et al.11 have reported the postmortem case of a 2-year-old girl who had been found unresponsive at home and later died in spite of intensive medical treatment. She showed several bruises of different colors in multiple suspicious locations, petechial hemorrhages, and also there had been an anonymous report of child abuse one month before she died. By autopsy, an unrecognised ALL was diagnosed, which might have been the reason for the notifiable bruising leading to the anonymous report, but there had not been any medical examination or laboratory control during lifetime. However, in a case described by Tattoli et al.12, a boy of 4 months had died with suspicion of neglect and in a state of severe malnutrition and dehydration, but without any cutaneous findings that could indicate physical child abuse. Here, autopsy revealed an ALL as cause of death. Nadjem et al. reported the case of a 4-year-old girl with petechial bruising in multiple areas susceptive to abuse, whereby the diagnosis ALL could readily be made after admission using laboratory investigation. 10 And a case of AML in a 3 year-old girl had been mistaken for child abuse with symptoms of ecchymotic lesions and weight loss with laboratory proven pancytopenia. 13
So far this case is an exception, with the phenomenon of there being widespread laboratory diagnosis during first hospitalization, ruling out relevant bleeding or hematological disorders, but with severe abnormalities being examined five months later, leading to the diagnosis ALL. In both instances, suspected injuries with a deficient medical history presumed possible cases of child abuse. The petechial nature of the bruises during the second admission, which can always be a sign of thrombocytopenia, led to repeated laboratory investigations. 14 Therefore, even in known cases of child abuse and follow-up, a thorough reevaluation is essential in every examination, as not only congenital but also acquired disorders can be the cause of bruising, which may individually lead to repeated laboratory testing. On the contrary, children with known coagulopathies can get abused as well, which leads to difficulties in differentiation between accidental and non-accidental injuries.15,16 Therefore, we consider a functional interdisciplinary approach between experienced pediatricians and forensic pathologists with special expertise in clinical forensic medicine as essential. Otherwise, findings that reinforce the suspicion of physical abuse, especially at the beginning of the examination, may lead to premature judgement, avoiding consequent differential diagnosing. In this report, we concentrate on cutaneous findings mimicking child abuse, though there are many other medical conditions which can lead to mistakenly suspected abuse. 14 Because the problem of mistaken child abuse is very sensitive, there have been some publications analyzing cohorts of children with suspected maltreatment and illustrating the medical conditions that were responsible for the false accusation. 1,2,14-17 The most frequent congenital bleeding disorders potentially mimicking child abuse are hemophilia and Von Willebrand disease (vWD). 2 Other medical conditions that frequently appear in different reports are Mongolian spots14-16, hemangioma14-16 and idiopathic thrombocytopenic purpura13-15. In the most comprehensive study so far 15, 2890 children with suspected abuse, from which 137 had at least one abuse-mimicking condition, have prospectively been evaluated. No less than 31 different causes for cutaneous findings were listed, but not a single case was associated with leukemia. Further possible causes are even more infrequent and only appear in few case reports, such as Schönlein-Henoch purpura15,18 or Ehlers-Danlos syndrome16,19. The procedure of hematologic evaluation in suspected child abuse is inconsistently performed in different clinics.1 A pediatrician should implement a basic laboratory examination, and if there are no pathological findings, but the suspicion of bleeding disorder is still present, he would have to consult a pediatric hematologist. In a recent study20, an initial testing panel for bruising
has
been recommended,
containing prothrombin time,
activated partial
thromboplastin time, vWF antigen, vWF activity (Ristocetin cofactor), factor-VIII level, factor-IX level and a complete blood count (CBC) with platelet count. Other authors21 recommend additional testing of thrombin time, factor-XIII level and PFA-100, which might be tested in a second panel. With these parameters, an adequate quantity of potential medical bleeding disorders, including the aforementioned most frequent ones, could either be diagnosed or ruled out. The petechial nature of the bruising was an important suggestion for repeated blood measurements, as this is indicative for hematological diseases. 10 Repeated CBC testing would surely reveal the ALL during second admission, so the guideline-based medical treatment could immediately be started and a rare but, if left untreated, lifethreatening disease could be spotted in good time.
Conclusion ALL in childhood is a rare disease that needs to be diagnosed as fast as possible to allow lifesaving medical treatment. Bruising due to this malignant illness can be mistaken for child maltreatment, delaying therapy and causing legal problems for parents and guardians as well as the child.
It is crucial to have effective communication and interaction between
pediatricians and forensic pathologists to differentiate between accidental and non-accidental injuries and to arrange the necessary supportive examinations, including an initial laboratory blood test to exclude frequent bleeding disorders, especially if punctate bleedings are visible. Because children known for possible physical abuse can acquire bleeding disorders, and patients with acquainted bleeding disorders can be the targets of such abuse, too, it is of the utmost importance after hospital admission to reevaluate every child exposed to suspected child abuse and to avoid ‘tunnel vision’ in the on-going assessment of those young patients previously diagnosed with abusive type injuries.
Compliance with Ethical Standards. Ethics: This article does not contain any studies with human or animal participants performed by any of the authors. Conflicts of Interest: The authors declare that they have no conflict of interest. Acknowledgments: We want to thank Mr. Jakob Anselm for his careful support in language editing.
References 1 Paroskie A, Carpenter SL, Lowen DE, Anderst J, DeBaun MR, Sidonio RF Jr (2014) A two-center retrospective review of the hematologic evaluation and laboratory abnormalities in suspected victims of non-accidental injury. Child Abuse Negl 38:1794-1800 2 Jackson J, Carpenter S, Anderst C (2012) Challenges in the evaluation for possible abuse: presentations of congenital bleeding disorders in childhood. Child Abuse Negl 36:127-134 3 Mudd SS, Findlay JS (2004) The cutaneous manifestations and common mimickers of physical child abuse. J Pediatr Health Care 18:123-129 4 Kodner C, Wetherton A (2013) Diagnosis and management of physical abuse in children. Physician 88:669-675
Am Fam
5 Imbach P (2005) Acute lymphoblastic leukemia. In: Pediatric Oncology, Springer-Verlag Berlin Heidelberg, p. 11-28 6 Kaatsch P, Spix C (2015) German childhood cancer registry – annual report (1980-2014). Institute for Medical Biostatistics, Epidemiology and Informatics, Johannes Gutenberg-University Mainz. 7 Bundesministerium des Inneren (2015), Polizeiliche Kriminalstatistik. https://www.bmi.bund.de/SharedDocs/Downloads/DE/Broschueren/2016/pks-2015.pdf?_blob= publicationFile (accessed 12.12.16) 8 Hunger SP, Mullighan CG (2015) Acute lymphoblastic leukemia in children. N Engl J Med 373:1541-1552 9 Department of Health & Human Services USA (2016). Child maltreatment 2014. https://www.acf.hhs.gov/sites/default/files/cb/cm2014.pdf (accessed 12.12.16) 10 Nadjem H, Sutor AH (1991) Hämatome bei akuter Leukose – Verdachtsdiagnose einer Kindesmißhandlung. Beitr Gerichtl Med 49:227-231 11 McClain JL, Clark MA, Sandusky GE (1990) Undiagnosed, untreated acute lymphoblastic leukemia presenting as suspected child abuse. J Forensic Sci 35:735-739 12 Tattoli L, Leonardi S, Carabellese S, Solarino B (2012) Acute lymphoblastic leukemia misdiagnosed as lethal child neglect. Rom J Leg Med 20:111-116 13 Scimeca PG, Cooper LB, Sahdev I (1996) Suspicion of child abuse complicating the diagnosis of bleeding disorders. Pediatr Hematol Oncol 13:179-182 14 Wheeler DM, Hobbs CJ (1988) Mistakes in diagnosing non-accidental injury: 10 years' experience. Br Med J 296:1233-1236
15 Schwartz KA, Metz J, Feldman K, Sidbury R, Lindberg DM, the ExSTRA Investigartors (2014) Cutaneous findings mistaken for physical abuse: present but not pervasive. Pediatr Dermatol 31:146155 16 Wardinsky TD, Vizcarrondo FE, Cruz BK (1995) The mistaken diagnosis of child abuse: A threeyear USAF Medical Center analysis and literature review. Mil Med 160:15-20 17 O’Hare AE, Eden OB (1984) Bleeding disorders and non-accidental injury. Arch Dis Child 59:860864 18 Brown J, Melinkovich P (1986) Schönlein-Henoch purpura misdiagnosed as suspected child abuse: a case report and literature review. JAMA 256:617-618 19 Castori M (2015) Ehlers–Danlos syndrome(s) mimicking child abuse: is there an impact on clinical practice? Am J Med Genet C 169:289-292 20 Anderst JD, Carpenter SL, Abshire TC, Section on Hematology/Oncology and Committee on Child Abuse and Neglect of the American Academy of Pediatrics (2013) Evaluation for bleeding disorders in suspected child abuse. Pediatrics 131:e1314-e1322 21 Minford AM, Richards EM (2010) Excluding medical and haematological conditions as a cause of bruising in suspected non-accidental injury. Arch Dis Child Educ Pract Ed 95:2-8
Figure legends
Fig. 1: Frontal photograph of the face with several notable bruises varying in intensity (taken during first admission to hospital).
Fig. 2: Picture of the lower abdomen with extensive excoriations and a surrounding bruising as well as healing rhagades around the root of the penis (taken during first admission).
Fig. 3: Lateral photograph of the left half of the face with slightly streaky appearance of the bruises and clearly visible petechial hemorrhages (taken during second admission to hospital).
Fig. 4: Picture of the left half of the bruised back with numerous single punctate bleedings (taken during second admission).
Tables Table 1. Laboratory findings during admission Hemoglobin (normal: 6.7-7.9 mmol/l) Hematocrit (normal: 0.34-0.4 l/l) Leucocytes (normal: 5-12 Gpt/l) Thrombocytes (normal: 140-360 Gpt/l) Retikulocytes (normal: 4.8-16.4/1000) Lymphocytes (normal: 13-55 %) Blasts (normal: negative) Atypical lymphocytes reactive (normal: negative) Granulocytes unsegmented (normal: 3-5 %) Granuloytes segmented (normal: 30-75 %) Anisocytosis
First admission 7.6 mmol/l
Second admission 4.8 mmol/l -
0.38 l/l
0.23 l/l -
6.4 Gpt/l
22.2 Gpt/l +
264 Gpt/l
28 Gpt/l 6.0/1000
52.3 %
76.0 % + 75.5 % + 6%+ 1.1 % 2.7 % ++
During the first investigation the following laboratory values were collected: Quick (98 %), aPTT (32.5 s), vWF antigen (77 %), Ristocetin cofactor activity (74 %), factor-VIII activity (91.4 %), factor-XIII activity (135 %), PFA collagen/ADP (105 s) and PFA collagen/epinephrine (138 s) to exclude a clotting disorder. All investigations resulted in normal ranges. The lymphomonocytic hemogram revealed an absolute neutropenia (0.56) during second admission. Pathological laboratory values are presented in bold print.
Highlights:
physicians needs to be familiar with medical conditions that can simulate maltreatment
interdisciplinary teamwork is necessary to match all investigation results with the present history
petechial nature of bruisings are important suggestions for hematological diseases
initial laboratory blood tests are necessary in context of non-accidental injuries