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Patients with factitious disorder seek to be cared for despite the lack of an underlying illness. To obtain "the sick role" they fake symptoms, fabricate history and manipulate their bodies and medical investigations to simulate a condition that will require medical or surgical care. Unlike patients who are seeking a reward—e.g. workman's compensation, or narcotics, their goal is solely to receive emotional support and medical attention.Despite the passage of 60 years since Asher first described factitious behaviour and labelled it Munchausen's syndrome, the accurate diagnosis of factitious disorder is still as challenging for clinicians today as it was in 1951.1 As a psychiatric condition that is usually seen by non-psychiatrists, it is under-recognized and under-appreciated in terms of its contribution to unnecessary morbidity and mortality as well as the cost to healthcare systems.Factitious disorder is usually first suspected when inexplicable laboratory results are noted in the course of a prolonged clinical investigation.2 Therefore, it is essential that clinicians be aware of the state-of-the-art techniques available to diagnose illness fabrication in the context of factitious disorder. Figure 1. Diagnostic criteria DSM-IV Diagnostic criteria for factitious disorder Intentional production or feigning of physical or psychological signs or symptoms. The motivation for the behaviour is to assume the sick role. External incentives for the behaviour (such as economic gain, avoiding legal responsibility, or improving physical well-being, as in Malingering) are absent. Surveys demonstrate that physicians across medical specialties are uncomfortable with diagnosing factitious disorder.3 Estimates of the incidence of factitious disorder among general hospital admissions range from 0.6% to 1.3%.3-5 Another report indicated that 3% of non-psychiatric hospital admissions over an 8-year period were by patients who had no known organic basis for their complaint.6 Other studies looking at specific problems such as fever of unknown origin have found a factitious basis for 3.5%-9.3% of cases.7,8 These numbers presumably represent a fraction of the cases that actually occur, since they do not include those who are not suspected or never detected. Factitious disorder not only impacts the doctor-patient relationship, it also results in a financial burden on the healthcare system. From case reports, we know patients with factitious disorder often undergo lengthy hospital stays and numerous tests and procedures before their activities are recognised. With advances in technology, there is both an increase in our diagnostic armamentarium as well as a greater expectation that we will obtain a diagnosis in a rapid fashion. Because factitious presentations will not make sense in a traditional medical context—wounds that do not heal, diarrhoea without an apparent cause, blood sugars that continue to be low despite treatment—most clinicians will assume that they are missing the diagnosis and pursue increasingly obscure (and often expensive or invasive) workups. Methods Definitions Eligibility criteria for inclusion in the systematic review: Studies of patients who fabricated illness, where their fabrication was detected by the use of laboratory or technical means. Technical means—This included any laboratory or procedural test that could be ordered from a hospital laboratory or a reference laboratory, or a reproducible test that involved technology or equipment that should be available at an academic medical centre through medical, neurological, surgical or pathology specialty and sub-specialty services in the first world. Factitious disorder—For the purposes of this review, a patient with factitious disorder is defined as a person who intentionally feigns or manufactures symptoms or signs of disease for the purposes of obtaining medical care and without other external motives for their behaviour. We intentionally exclude other conditions such as malingering, conversion disorder, hypochondriasis, noncompliance, suicidal acts, admitted self-harm behaviours, iatrogenic misadventures, and errors by laboratories or mistakes of interpretation by clinicians. The authors performed a systemic review of the literature to evaluate laboratory and technical methods that can assist diagnosticians in recognizing factitious disorder. We evaluated a possible 3104 citations to develop a state of the art guide for clinicians to use in diagnosing factitious disorder. The focus of our review was solely on the use of laboratory and technical methods (including the use of radiology, endoscopy, neurodiagnostic tools, and histology, among other modalities) to recognize when patients may have manipulated their clinical presentation to assume the sick role. Primary search string—((Factitious - (as MeSH term and Keyword)) OR (Munchhausen) OR (Munchausen—(as MeSH term and Keyword)) OR (fantastica) OR (dermatitis artefacta)). The search was current through January 2010. Note that adding the MeSH term or keyword of "somatoform" increases the yield to 9763 articles but did not appear to offer any advantage when this search was further developed or subcategories were added. "Psychogenic" was an exception to search terms as it did bring additional cases and reports to light, but only in the field of neurology where it is applied to non-epileptic seizures and to movement disorders without an identified organic basis. Additional searches were performed using variants of: autodestructive, somatic, somatisation, hypochondr*, faking, fabricated, faked, fictitious, artefacta, pseudologia, Asher, Ganser's, "by proxy." However none of these search strings as keywords (or MESH terms) resulted in additional relevant articles. Three articles were found in the cited bibliographies of papers on factitious disorder that were not found in literature searches. Databases reviewed—This search string in Medline (PubMed) resulted in 3104 articles. 1088 involved primary reports of factitious manifestations of specific disorders. 190 of these articles offered unique and applicable information. An additional search in PsyINFO did not offer any articles that addressed novel issues of clinical diagnostic methodology. We also consulted with multiple specialists from each medical and surgical specialty - at several major medical centres in the United States and New Zealand - for additional examples of useful tests not covered in the literature, but none were suggested. The European literature database EMBASE was also reviewed but not systematically. No additional articles were found using checks of above terminology. Articles without English abstracts were not investigated if their title did not appear to be directly relevant. A conscious decision was made not to survey the forensic pathology or biochemistry literature for discussions of techniques not previously applied to factitious disorder. This was done to limit the review to articles of significance to practicing clinicians, most of whom will not have access to specialized laboratories services. In general, the tests discussed should be available at an academic medical centre, reference laboratory or through normal consultation with medical and surgical specialists and clinical pathologists. Results The table below represents the information gained from the 190 articles that offered methods for the diagnosis of factitious disorder. Table 1. Tools for diagnosing factitious disorder by speciality and condition SYMPTOM LABORATORY TEST COMMENTS Cardiovascular Angina Definitive test: coronary angiography. Also consider: stress test, ECG, Echocardiogram for wall motion abnormalities.14 History of prior myocardial infarction or cardiac bypass does NOT exclude factitious presentation- may represent the patient fabricating prior symptoms. Arrhythmia Consider indirect dysrhythmia though manipulated electrolytes (Mg, K).15Supervise telemetry lead placement to avoid manipulation.16,17 Digitalis, beta-blockers and calcium channel blockers can be measured in serum.18 Arrhythmias have also been reported in patients with surreptitious laxative or thyroxine abuse (see below). Aortic dissection In patients reportedly unable to receive CT aortogram with contrast or MRI, consider transthoracic echocardiogram.19,20 Patient's goal may be thoracotomy. Patients have reported an allergy to radiography contrast prohibiting CT imaging. Also allergy to gadolinium or shrapnel residue in their body prohibiting MRI. Hypotension Serum assays for beta-blockers and calcium channel blockers. Electrochemiluminescence assays detect atenolol and metoprolol in urine samples.21,22 Capillary electrophoresis with electrochemiluminescence detection - assays developed to detect doping in sports. Hypertension Serum or urine assay for pseudoephedrine.23,24pheochromocytoma can also be simulated.25,26 Valsalva manoeuvre may be used by the patient during BP measurement to produce transient HTN. Dermatologic Chelitis granulomatosa Liver and lymph node biopsies may show histiocytes that contain Polyvinylpyrrolidone (PVP) suggesting self-inoculation. PVP, a polymer, is used in hair sprays, skin care products, fruit juices, Dermatitis artefacta, chelitis, Subcutaneous emphysema Punch biopsy with histopathology- may reveal evidence of mechanical trauma with areas of necrosis and extravasation of RBCs.27 Imaging or skin exam can note needle tracks for subcutaneous air.28 Erythematous lesion, pemphigus Apply alcohol to lesion.29,30 Direct immunofluorescence.29 Herpes Zoster Negative viral PCR.31 Onychodystrophy Microscopy.32 Nail file to replicate symptoms. Scabies Scabies PCR, microscopy.33 Endocrine Cushing's syndrome High-pressure liquid chromatography (HPLC) used to distinguish exogenous vs. endogenous glucocorticoids.34Cortisol and corticosterone are co-secreted, so both should be checked since corticosterone will not be elevated if cortisol is surreptitiously added to urine samples.35 Surreptitious addition of hydrocortisone requires measurement of upstream metabolites to check for evidence of suppressed pituitary secretion of ACTH. Hyperaldosteronism Glycyrrhizic acid can be detected in serum.36 The ingestion of black liquorice has gained particular notoriety on the internet. The sweetener used to make licorice, glycyrrhizic acid can lead to treatment-resistant hypokalemia, metabolic alkalosis and hypernatremia. Hyperthyroidism TSH, T3, free T4, thyroglobulin, and thyroid autoantibody. Some recommend 24h radioiodine uptake testing.37 During thyroid storm factitious hyperthyroidism is the only aetiology in which TSH will be low.38 Some herbal medications contain thyroid hormones. Serum thyroglobulin may less useful as 10-20% of people have anti-thyroglobulin antibodies that may affect thyroglobulin measurement. Hypoglycaemia Serum insulin, C-peptide, and proinsulin levels, assays for metformin, meglitinides, sulfonylureas.39 Novel incretin analogue exenatide and amylin analogue pramlintide not routinely included in hypoglycaemic drug screens.40 Also consider manipulation of testing strips.41 Urine can be more sensitive than serum and may remain positive for a longer period.42,43 Anti-insulin antibodies no longer useful as more human recombinant insulin is used. Also C-peptide is cleared renally and will be elevated in renal failure. Pheochromocytoma Serum chromogranin A useful to identify true pheochromocytoma. 44 Meta-iodobenzylguanidine (nuclear scan is probably the gold standard.45Vanillylmandelic acid (VMA) should not be used for suspected factitious pheochromocytoma because vanilla extract or foods high in vanillin can elevate VMA.46 Agents to mimic pheochromocytoma symptoms include self-administration of epinephrine, metaraminol, and isoproternol.47,48 patients can use the Valsalva manoeuvre to produce a symptom pattern suggestive of pheochromocytoma.25,26 Gastrointestinal Diarrhoea Surreptitious addition of water to stools detected by measuring faecal fluid osmolality - if less than 290 mosm\/kg, water or hypotonic solution may have been added to stool.49Consider 3-day stool collection for 200g\/day volume check.50,51 Urine screen for phenolphthaleins, anthraquinones, and bisacodyl plus stool screen for magnesium and phosphate.52 Urine and stool "laxative abuse" screens often need to be performed multiple times due to intermittent laxative use by patients and low sensitivity of the tests. Gastrointestinal (GI) bleeding Factitious bleeding suggested when nasogastric tube shows blood but no cause found on oesophagogastroduodeno-scopy.53Colonoscopy is less sensitive to elucidate lower GI bleeding.54 The "single-stripe" sign on colonoscopy may indicate non-steroidal anti-inflammatory abuse, which can be detected on high performance liquid chromatography (HPLC).55 Ingestion of salicylates can also cause factitious lower GI bleeds.56Radiolabelling only useful in a patient injecting themselves with blood they had obtained from transfusions in-hospital; discovered when rectal blood was found not to be radiolabelled after a radio-isotope injection.57 Nausea\/vomiting When produced by ipecac consumption, measure serum or urine emetine levels (detectable by HPLC).58Elevated creatine kinase, leukocytosis, and transaminitis also associated with ipecac toxicity.59 After vomiting episodes, clinicians should see low serum potassium, low chloride after acute vomiting or prolonged episodes of vomiting. Excess ipecac induces myopathic toxicity including skeletal muscle weakness and hypotonia and cardiomyopathy with dysrhythmias, T-wave abnormalities, and prolonged QT interval.60-62 Pseudo-obstruction Detect loperamide or another motility slowing agent by HPLC of blood or stool.63 Gynaecology and Obstetrics False Ectopic Pregnancy Self-injection of human chorionic gonadotropin (hCG) has been reported. This led to a negative urine beta-hCG and negative ultrasound. Also subsequent serum beta-hCG levels were widely varying.64 Vaginal Discharge Typically the fluids have an inconsistent pH or the vaginal wall shows evidence of trauma\/abrasion in patients denying intercourse or instrumentation. Hematologic Anaemia\/Bleeding Examination may show evidence of venipuncture or instrumentation, particularly of orifices or the genital-urinary tract or gastrointestinal tract on endoscopy.1 Anticoagulation For patients not known to be on warfarin, administer vitamin K, and then re-check PT\/INR. Warfarin can be assayed directly but warfarin derivatives such as the rodenticide brodifacoum require use of HPLC.65,66 For patients on warfarin, there can be "false-resistance" to warfarin that requires extensive clinical input and attention. This must be cautiously approached as genetics can play a large role. If vitamin K and plasma Warfarin levels are irregular, consider genetic testing if there is no indication of factitious behaviour.67 Prolonged PTT but normal reptilase time suggest presence of heparin. Another test is to add protamine sulphate or an ion-exchange resin to the blood sample which will indicate the presence of exogenous heparin.68 The most common hematologic factitious disorder is surreptitious anticoagulation abuse. Aplastic Anaemia This has been provoked by the ingestion of alkylating agents such as busulfan or other chemotherapy agents.69,70 Sickle Cell Disease Confirmation with haemoglobin electrophoresis.71,72 Important for patients not known to local clinicians. Thrombocytopenia\/ITP (also see Rheumatologic-Purpura) Purpura and ITP Feigned by quinidine ingestion- check serum quinidine level.73 Isolated thrombocytopenia has been caused by quinine ingestion.74 Infectious diseases Bacteraemia Polymicrobial bacteraemia or unusual organisms in blood cultures should raise suspicion.75,76 Case reports note stool flora, pet flora as most common exogenous material. Fever Directly observed temperature measurement using electronic thermometer. Ensure no recent ingestion of hot beverages, warm wax or wet cotton in ears. In 1979, 9% of patients presenting to an NIH study on fever of unknown origin were found to be suffering from factitious disorder.7 HIV\/AIDS Repeat HIV ELISA and Western blot, check viral load for acute HIV.77 Patient with normal CD4 count and undetectable viral load can claim suppression with anti-retrovirals. But antibody should still be positive. Wounds Apply fluorescein or tetracycline to wound, then examine hands\/nails for fluorescence. Non-healing wounds will heal when casted- but this can be circumvented by patients. Substances introduced into wounds include: human\/animal faeces, household toxins, aquarium water, foreign bodies, milk and others.78,79 Neurologic Movement disorders EMG and EEG reveal inconsistent amplitude patterns in factitious tremors and myoclonus.80 Dopaminergic drugs including antipsychotics may be taken to induce Parkinsonian symptoms. Multiple sclerosis MRI brain demonstrating at least 2 different regions of white matter change CSF with mild lymphocytosis, oligoclonal bands in IgG region. CSF protein electrophoresis is 90% sensitive in pts with active MS symptoms. Non-epileptiform seizures Serum prolactin level at baseline (near onset of epileptiform activity) then 20 minutes later.81 However this can be normal in partial-seizures and elevated in epilepsy.81 Video EEG useful but this can miss frontal lobe seizures which have movements that can suggest factitious behaviour such as pelvic thrusting and cycling movements.82,83 One estimate suggests that 15-30% of the patients presenting to epilepsy clinics with refractory epilepsy are psychogenic in nature.84 Most of these patients are unlikely to have factitious disorder. Nephrologic\/Urologic Diuretic Abuse\/Bartter syndrome Urine assays can detect furosemide, torsemide, and hydrochlorothiazide. HPLC can detect Furosemide and other diuretics.85,86 Bartter syndrome is a rare inherited defect in the ascending loop of Henle, there are at least 6 reports of factitious presentations of this condition.87 Goodpastures Syndrome See haematuria and haemoptysis sections. One patient appeared in 3 different peer reviewed articles.88-90 Haematuria Direct observation of urine collection to ensure blood or iodine not added to sample. Three tube te

Summary

Abstract

Aim

To assist clinicians in the diagnosis of factitious disorder.

Method

This is a systematic review of the role of laboratory, radiologic, procedural, and pathological modalities to assist in the diagnosis of factitious disorder (Munchausens syndrome). The review evaluated 3104 article titles and abstracts that were identified from MEDLINE as of January 2010.

Results

We found 190 articles that demonstrated techniques that will assist clinicians in recognizing fabricated manifestations of disease. The results are divided into 13 areas of clinical medicine for easy reference. They are further sub-divided by the diseases or conditions that patients have been reported to simulate and the diagnostic techniques suggested by the literature in each case.

Conclusion

Factitious disorder is difficult to diagnose and may present as a wide array of fabricated conditions, but there are a range of laboratory and technical means available to assist clinicians in the 21st Century.

Author Information

Christopher A Kenedi, Consultant, Departments of General Medicine and Liaison Psychiatry, Auckland City Hospital, Auckland, New Zealandand Adj Associate of Internal Medicine and Psychiatry, Duke University Medical Center, Durham, NC, USAand Hon Sr Lecturer. Auckland University School of Medicine, Auckland, New Zealand; Mary Hoffa, Jeremy D Harrison, Residents, Departments of Medicine and Psychiatry, Duke University Medical Center, Durham, NC, USA; Kristen G. Shirey, Joseph Zanga, Clinical Associates in Medicine and Psychiatry, Duke University Medical Center, Durham, NC, USA; Xavier A Preudhomme, Assistant Professors of Internal Medicine and Psychiatry, Duke University Medical Center, Durham, NC, USA; Jonathan C Lee, Associate Medical Director, Farley Center at Williamsburg Place, Williamsburg, VA, USA

Acknowledgements

We thank Harold Goforth MD and Jacques Wallach MD for their assistance.

Correspondence

Christopher A Kenedi, Liaison Psychiatry, Level 4 Support Building, Private Bag 92024, Auckland, 1142 New Zealand. Fax: +64 (0)9 3078945

Correspondence Email

Bluedevilkiwi-factitious@yahoo.com

Competing Interests

None.

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Voluntary stimulus-sensitive jerks and jumps mimicking myoclonus or pathological startle syndromes. Mov Disord. 1992;7(3):257-262.Trimble MR. Serum prolactin in epilepsy and hysteria. . Br Med J. 1987;2:1682-1684.Bye AM, Nunan J. Video EEG analysis of non-ictal events in children. Clin Exp Neurol. 1992;29:92-98.French J. Pseudoseizures in the era of video-electroencephalogram monitoring. Curr Opin Neurol. Apr 1995;8(2):117-120.Bodde NM, Brooks JL, Baker GA, Boon PA, Hendriksen JG, Aldenkamp AP. Psychogenic non-epileptic seizures--diagnostic issues: a critical review. Clin Neurol Neurosurg. Jan 2009;111(1):1-9.D'Avanzo M, Santinelli R, Tolone C, Bettinelli A, Bianchetti MG. Concealed administration of frusemide simulating Bartter syndrome in a 4.5-year-old boy. Pediatr Nephrol. Dec 1995;9(6):749-750.Tran HA. A woman with malaise and hyponatremia. Hyponatremia factitia (Munchausen syndrome) secondary to desmopressin use. Arch Pathol Lab Med. Feb 2006;130(2):e15-18.Sekine K, Kojima I, Fujita T, Uchino K, Isozaki S, Ogata E. Factitious Bartter's syndrome induced by surreptitious intake of furosemide. Endocrinol Jpn. Oct 1982;29(5):653-657.Duffy TP. The Red Baron. N Engl J Med. Aug 6 1992;327(6):408-411.Ifudu O, Kolasinski SL, Friedman EA. Brief report: kidney-related Munchausen's syndrome. N Engl J Med. Aug 6 1992;327(6):388-389.Flynn J. Munchausen syndrome. N Y State J Med. 1992;92:301-305.Abrol RP, Heck A, Gleckel L, Rosner F. Self-induced hematuria. J Natl Med Assoc. Feb 1990;82(2):127-128.Baker MD, Baldassano RN. Povidone iodine as a cause of factitious hematuria and abnormal urine coloration in the pediatric emergency department. Pediatr Emerg Care. Dec 1989;5(4):240-241.Fukuhara S, Kawamura N, Kakuta Y, Imazu T, Hara T, Yamaguchi S. [Case of self mutilation of urethra in a Munchausen's syndrome patient]. Hinyokika Kiyo. Nov 2007;53(11):829-831.Schmidt F, Strutz F, Quellhorst E, Muller GA. Nephrectomy and solitary kidney biopsy in a patient with Munchausen's syndrome. Nephrol Dial Transplant. May 1996;11(5):890-892.Reich JD, Hanno PM. Factitious renal colic. Urology. Dec 1997;50(6):858-862.Gault MH, Campbell NR, Aksu AE. Spurious stones. Nephron. 1988;48(4):274-279.Attar K, Lee G, Rowe E, Hudd C. The secret of the phantom stone: a case report. Int Urol Nephrol. 2004;36(1):27-28.Tojo A, Nanba S, Kimura K, et al. Factitious proteinuria in a young girl. Clin Nephrol. Jun 1990;33(6):299-302.Mitas JA, 2nd. Exogenous protein as the cause of nephrotic-range proteinuria. Am J Med. Jul 1985;79(1):115-118.Levenson JL, Chafe W, Flanagan P. Factitious ovarian cancer: feigning via resources on the internet. Psychosomatics. Jan-Feb 2007;48(1):71-73.Feldman MD, Peychers ME. Legal issues surrounding the exposure of \"Munchausen by Internet\". Psychosomatics. Sep-Oct 2007;48(5):451-452.Feldman MD. Prophylactic bilateral radical mastectomy resulting from factitious disorder. Psychosomatics. Nov-Dec 2001;42(6):519-521.Feldman MD, Hamilton JC. Mastectomy resulting from factitious disorder. Psychosomatics. Jul-Aug 2007;48(4):361.Grenga TE, Dowden RV. Munchausen's syndrome and prophylactic mastectomy. Plast Reconstr Surg. Jul 1987;80(1):119-120.Rosenberg MW, Hughes LE. Artefactual breast disease: a report of three cases. Br J Surg. Jul 1985;72(7):539-541.Warrens AN, Ron MA, Dawling S. Positive diagnosis of self-medication with homatropine eye drops. Br J Psychiatry. Jan 1990;156:124-125.Rosenberg PN, Krohel GB, Webb RM, Hepler RS. Ocular Munchausen's syndrome. Ophthalmology. Aug 1986;93(8):1120-1123.Lembach RG, Ringel DM. Factitious bilateral crystalline keratopathy. Cornea. Jul 1990;9(3):246-248.Minemura K, Nagahara M, Kaburaki T, et al. [Case of recurrent fungal endophthalmitis with suspected Munchausen syndrome]. Nippon Ganka Gakkai Zasshi. Mar 2006;110(3):188-192.Mushtaq B, Kumar V, Saeed T, Bacon PA, Murray PI. Self-inflicted anterior scleritis. Eye. Jan 2003;17(1):107-108.Zamir E, Read RW, Rao NA. Self-inflicted anterior scleritis. Ophthalmology. Jan 2001;108(1):192-195.Pokroy R, Marcovich A. Self-inflicted (factitious) conjunctivitis. Ophthalmology. Apr 2003;110(4):790-795.Baskin DE, Stein F, Coats DK, Paysse EA. Recurrent conjunctivitis as a presentation of munchausen syndrome by proxy. Ophthalmology. Aug 2003;110(8):1582-1584.Kapoor HK, Jaison SG, Chopra R, Kakkar N. Factitious keratoconjunctivitis. Indian J Ophthalmol. Dec 2006;54(4):282-283.Vaiman M, Shoval G, Gavriel H. The electrodiagnostic examination of psychogenic swallowing disorders. Eur Arch Otorhinolaryngol. Jun 2008;265(6):663-668.Egan AJ, Tazelaar HD, Myers JL, Abell-Aleff PC. Munchausen syndrome presenting as pulmonary talcosis. Arch Pathol Lab Med. Aug 1999;123(8):736-738.Hendrix S, Sale S, Zeiss CR, Utley J, Patterson R. Factitious Hymenoptera allergic emergency: a report of a new variant of Munchausen's syndrome. J Allergy Clin Immunol. Jan 1981;67(1):8-13.Patterson R, Schatz M. Factitious allergic emergencies: anaphylaxis and laryngeal \"edema\". J Allergy Clin Immunol. Aug 1975;56(2):152-159.Croft PR, Racz MI, Bloch JD, Palmer CH. Autopsy confirmation of severe pulmonary interstitial fibrosis secondary to Munchausen syndrome presenting as cystic fibrosis. J Forensic Sci. Sep 2005;50(5):1194-1198.Leonard A, Leal T, Godding V, Villanueva P, Wallemacq P, Lebecque P. Sweat potassium concentration may help to identify falsification of sweat test: a case report. Clin Biochem. Sep 2008;41(13):1110-1112.Rusakow LS, Gershan WM. Hemoptysis and Munchausen syndrome. Chest. Oct 1994;106(4):1308-1309.Kokturk N, Ekim N, Aslan S, Kanbay A, Acar AT. A rare cause of hemoptysis: factitious disorder. South Med J. Feb 2006;99(2):186-187.Baktari JB, Tashkin DP, Small GW. Factitious hemoptysis. Adding to the differential diagnosis. Chest. Mar 1994;105(3):943-945.Burkle FM, Jr., Calabro JJ, Parks FB. Munchausen's syndrome presenting as respiratory failure requiring intubation. Ann Emerg Med. Feb 1987;16(2):203-208.Cole RP, Walter KL. Factitious intrinsic PEEP in a patient with respiratory failure. Respiration. 2001;68(5):555.Klaassen FA, Schober P, Schwarte LA, Boer C, Loer SA. Acute respiratory failure leading to emergency intubation: an unusual manifestation of Munchausen's syndrome. Resuscitation. Dec 2007;75(3):534-539.Samaniah N, Horowitz J, Buskila D, Sukenik S. An unusual case of factitious arthritis. J Rheumatol. Sep 1991;18(9):1424-1426.Apfelbaum JD, Williams HJ. Factitious simulation of systemic lupus erythematosus. West J Med. Mar 1994;160(3):259-261.Fonseca E, Rubio G. Factitious systemic lupus erythematosus. Lupus. Jun 1993;2(3):195-197.Archer-Dubon C, Orozco-Topete R, Reyes-Gutierrez E. Two cases of psychogenic purpura. Rev Invest Clin. Mar-Apr 1998;50(2):145-148.

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Patients with factitious disorder seek to be cared for despite the lack of an underlying illness. To obtain "the sick role" they fake symptoms, fabricate history and manipulate their bodies and medical investigations to simulate a condition that will require medical or surgical care. Unlike patients who are seeking a reward—e.g. workman's compensation, or narcotics, their goal is solely to receive emotional support and medical attention.Despite the passage of 60 years since Asher first described factitious behaviour and labelled it Munchausen's syndrome, the accurate diagnosis of factitious disorder is still as challenging for clinicians today as it was in 1951.1 As a psychiatric condition that is usually seen by non-psychiatrists, it is under-recognized and under-appreciated in terms of its contribution to unnecessary morbidity and mortality as well as the cost to healthcare systems.Factitious disorder is usually first suspected when inexplicable laboratory results are noted in the course of a prolonged clinical investigation.2 Therefore, it is essential that clinicians be aware of the state-of-the-art techniques available to diagnose illness fabrication in the context of factitious disorder. Figure 1. Diagnostic criteria DSM-IV Diagnostic criteria for factitious disorder Intentional production or feigning of physical or psychological signs or symptoms. The motivation for the behaviour is to assume the sick role. External incentives for the behaviour (such as economic gain, avoiding legal responsibility, or improving physical well-being, as in Malingering) are absent. Surveys demonstrate that physicians across medical specialties are uncomfortable with diagnosing factitious disorder.3 Estimates of the incidence of factitious disorder among general hospital admissions range from 0.6% to 1.3%.3-5 Another report indicated that 3% of non-psychiatric hospital admissions over an 8-year period were by patients who had no known organic basis for their complaint.6 Other studies looking at specific problems such as fever of unknown origin have found a factitious basis for 3.5%-9.3% of cases.7,8 These numbers presumably represent a fraction of the cases that actually occur, since they do not include those who are not suspected or never detected. Factitious disorder not only impacts the doctor-patient relationship, it also results in a financial burden on the healthcare system. From case reports, we know patients with factitious disorder often undergo lengthy hospital stays and numerous tests and procedures before their activities are recognised. With advances in technology, there is both an increase in our diagnostic armamentarium as well as a greater expectation that we will obtain a diagnosis in a rapid fashion. Because factitious presentations will not make sense in a traditional medical context—wounds that do not heal, diarrhoea without an apparent cause, blood sugars that continue to be low despite treatment—most clinicians will assume that they are missing the diagnosis and pursue increasingly obscure (and often expensive or invasive) workups. Methods Definitions Eligibility criteria for inclusion in the systematic review: Studies of patients who fabricated illness, where their fabrication was detected by the use of laboratory or technical means. Technical means—This included any laboratory or procedural test that could be ordered from a hospital laboratory or a reference laboratory, or a reproducible test that involved technology or equipment that should be available at an academic medical centre through medical, neurological, surgical or pathology specialty and sub-specialty services in the first world. Factitious disorder—For the purposes of this review, a patient with factitious disorder is defined as a person who intentionally feigns or manufactures symptoms or signs of disease for the purposes of obtaining medical care and without other external motives for their behaviour. We intentionally exclude other conditions such as malingering, conversion disorder, hypochondriasis, noncompliance, suicidal acts, admitted self-harm behaviours, iatrogenic misadventures, and errors by laboratories or mistakes of interpretation by clinicians. The authors performed a systemic review of the literature to evaluate laboratory and technical methods that can assist diagnosticians in recognizing factitious disorder. We evaluated a possible 3104 citations to develop a state of the art guide for clinicians to use in diagnosing factitious disorder. The focus of our review was solely on the use of laboratory and technical methods (including the use of radiology, endoscopy, neurodiagnostic tools, and histology, among other modalities) to recognize when patients may have manipulated their clinical presentation to assume the sick role. Primary search string—((Factitious - (as MeSH term and Keyword)) OR (Munchhausen) OR (Munchausen—(as MeSH term and Keyword)) OR (fantastica) OR (dermatitis artefacta)). The search was current through January 2010. Note that adding the MeSH term or keyword of "somatoform" increases the yield to 9763 articles but did not appear to offer any advantage when this search was further developed or subcategories were added. "Psychogenic" was an exception to search terms as it did bring additional cases and reports to light, but only in the field of neurology where it is applied to non-epileptic seizures and to movement disorders without an identified organic basis. Additional searches were performed using variants of: autodestructive, somatic, somatisation, hypochondr*, faking, fabricated, faked, fictitious, artefacta, pseudologia, Asher, Ganser's, "by proxy." However none of these search strings as keywords (or MESH terms) resulted in additional relevant articles. Three articles were found in the cited bibliographies of papers on factitious disorder that were not found in literature searches. Databases reviewed—This search string in Medline (PubMed) resulted in 3104 articles. 1088 involved primary reports of factitious manifestations of specific disorders. 190 of these articles offered unique and applicable information. An additional search in PsyINFO did not offer any articles that addressed novel issues of clinical diagnostic methodology. We also consulted with multiple specialists from each medical and surgical specialty - at several major medical centres in the United States and New Zealand - for additional examples of useful tests not covered in the literature, but none were suggested. The European literature database EMBASE was also reviewed but not systematically. No additional articles were found using checks of above terminology. Articles without English abstracts were not investigated if their title did not appear to be directly relevant. A conscious decision was made not to survey the forensic pathology or biochemistry literature for discussions of techniques not previously applied to factitious disorder. This was done to limit the review to articles of significance to practicing clinicians, most of whom will not have access to specialized laboratories services. In general, the tests discussed should be available at an academic medical centre, reference laboratory or through normal consultation with medical and surgical specialists and clinical pathologists. Results The table below represents the information gained from the 190 articles that offered methods for the diagnosis of factitious disorder. Table 1. Tools for diagnosing factitious disorder by speciality and condition SYMPTOM LABORATORY TEST COMMENTS Cardiovascular Angina Definitive test: coronary angiography. Also consider: stress test, ECG, Echocardiogram for wall motion abnormalities.14 History of prior myocardial infarction or cardiac bypass does NOT exclude factitious presentation- may represent the patient fabricating prior symptoms. Arrhythmia Consider indirect dysrhythmia though manipulated electrolytes (Mg, K).15Supervise telemetry lead placement to avoid manipulation.16,17 Digitalis, beta-blockers and calcium channel blockers can be measured in serum.18 Arrhythmias have also been reported in patients with surreptitious laxative or thyroxine abuse (see below). Aortic dissection In patients reportedly unable to receive CT aortogram with contrast or MRI, consider transthoracic echocardiogram.19,20 Patient's goal may be thoracotomy. Patients have reported an allergy to radiography contrast prohibiting CT imaging. Also allergy to gadolinium or shrapnel residue in their body prohibiting MRI. Hypotension Serum assays for beta-blockers and calcium channel blockers. Electrochemiluminescence assays detect atenolol and metoprolol in urine samples.21,22 Capillary electrophoresis with electrochemiluminescence detection - assays developed to detect doping in sports. Hypertension Serum or urine assay for pseudoephedrine.23,24pheochromocytoma can also be simulated.25,26 Valsalva manoeuvre may be used by the patient during BP measurement to produce transient HTN. Dermatologic Chelitis granulomatosa Liver and lymph node biopsies may show histiocytes that contain Polyvinylpyrrolidone (PVP) suggesting self-inoculation. PVP, a polymer, is used in hair sprays, skin care products, fruit juices, Dermatitis artefacta, chelitis, Subcutaneous emphysema Punch biopsy with histopathology- may reveal evidence of mechanical trauma with areas of necrosis and extravasation of RBCs.27 Imaging or skin exam can note needle tracks for subcutaneous air.28 Erythematous lesion, pemphigus Apply alcohol to lesion.29,30 Direct immunofluorescence.29 Herpes Zoster Negative viral PCR.31 Onychodystrophy Microscopy.32 Nail file to replicate symptoms. Scabies Scabies PCR, microscopy.33 Endocrine Cushing's syndrome High-pressure liquid chromatography (HPLC) used to distinguish exogenous vs. endogenous glucocorticoids.34Cortisol and corticosterone are co-secreted, so both should be checked since corticosterone will not be elevated if cortisol is surreptitiously added to urine samples.35 Surreptitious addition of hydrocortisone requires measurement of upstream metabolites to check for evidence of suppressed pituitary secretion of ACTH. Hyperaldosteronism Glycyrrhizic acid can be detected in serum.36 The ingestion of black liquorice has gained particular notoriety on the internet. The sweetener used to make licorice, glycyrrhizic acid can lead to treatment-resistant hypokalemia, metabolic alkalosis and hypernatremia. Hyperthyroidism TSH, T3, free T4, thyroglobulin, and thyroid autoantibody. Some recommend 24h radioiodine uptake testing.37 During thyroid storm factitious hyperthyroidism is the only aetiology in which TSH will be low.38 Some herbal medications contain thyroid hormones. Serum thyroglobulin may less useful as 10-20% of people have anti-thyroglobulin antibodies that may affect thyroglobulin measurement. Hypoglycaemia Serum insulin, C-peptide, and proinsulin levels, assays for metformin, meglitinides, sulfonylureas.39 Novel incretin analogue exenatide and amylin analogue pramlintide not routinely included in hypoglycaemic drug screens.40 Also consider manipulation of testing strips.41 Urine can be more sensitive than serum and may remain positive for a longer period.42,43 Anti-insulin antibodies no longer useful as more human recombinant insulin is used. Also C-peptide is cleared renally and will be elevated in renal failure. Pheochromocytoma Serum chromogranin A useful to identify true pheochromocytoma. 44 Meta-iodobenzylguanidine (nuclear scan is probably the gold standard.45Vanillylmandelic acid (VMA) should not be used for suspected factitious pheochromocytoma because vanilla extract or foods high in vanillin can elevate VMA.46 Agents to mimic pheochromocytoma symptoms include self-administration of epinephrine, metaraminol, and isoproternol.47,48 patients can use the Valsalva manoeuvre to produce a symptom pattern suggestive of pheochromocytoma.25,26 Gastrointestinal Diarrhoea Surreptitious addition of water to stools detected by measuring faecal fluid osmolality - if less than 290 mosm\/kg, water or hypotonic solution may have been added to stool.49Consider 3-day stool collection for 200g\/day volume check.50,51 Urine screen for phenolphthaleins, anthraquinones, and bisacodyl plus stool screen for magnesium and phosphate.52 Urine and stool "laxative abuse" screens often need to be performed multiple times due to intermittent laxative use by patients and low sensitivity of the tests. Gastrointestinal (GI) bleeding Factitious bleeding suggested when nasogastric tube shows blood but no cause found on oesophagogastroduodeno-scopy.53Colonoscopy is less sensitive to elucidate lower GI bleeding.54 The "single-stripe" sign on colonoscopy may indicate non-steroidal anti-inflammatory abuse, which can be detected on high performance liquid chromatography (HPLC).55 Ingestion of salicylates can also cause factitious lower GI bleeds.56Radiolabelling only useful in a patient injecting themselves with blood they had obtained from transfusions in-hospital; discovered when rectal blood was found not to be radiolabelled after a radio-isotope injection.57 Nausea\/vomiting When produced by ipecac consumption, measure serum or urine emetine levels (detectable by HPLC).58Elevated creatine kinase, leukocytosis, and transaminitis also associated with ipecac toxicity.59 After vomiting episodes, clinicians should see low serum potassium, low chloride after acute vomiting or prolonged episodes of vomiting. Excess ipecac induces myopathic toxicity including skeletal muscle weakness and hypotonia and cardiomyopathy with dysrhythmias, T-wave abnormalities, and prolonged QT interval.60-62 Pseudo-obstruction Detect loperamide or another motility slowing agent by HPLC of blood or stool.63 Gynaecology and Obstetrics False Ectopic Pregnancy Self-injection of human chorionic gonadotropin (hCG) has been reported. This led to a negative urine beta-hCG and negative ultrasound. Also subsequent serum beta-hCG levels were widely varying.64 Vaginal Discharge Typically the fluids have an inconsistent pH or the vaginal wall shows evidence of trauma\/abrasion in patients denying intercourse or instrumentation. Hematologic Anaemia\/Bleeding Examination may show evidence of venipuncture or instrumentation, particularly of orifices or the genital-urinary tract or gastrointestinal tract on endoscopy.1 Anticoagulation For patients not known to be on warfarin, administer vitamin K, and then re-check PT\/INR. Warfarin can be assayed directly but warfarin derivatives such as the rodenticide brodifacoum require use of HPLC.65,66 For patients on warfarin, there can be "false-resistance" to warfarin that requires extensive clinical input and attention. This must be cautiously approached as genetics can play a large role. If vitamin K and plasma Warfarin levels are irregular, consider genetic testing if there is no indication of factitious behaviour.67 Prolonged PTT but normal reptilase time suggest presence of heparin. Another test is to add protamine sulphate or an ion-exchange resin to the blood sample which will indicate the presence of exogenous heparin.68 The most common hematologic factitious disorder is surreptitious anticoagulation abuse. Aplastic Anaemia This has been provoked by the ingestion of alkylating agents such as busulfan or other chemotherapy agents.69,70 Sickle Cell Disease Confirmation with haemoglobin electrophoresis.71,72 Important for patients not known to local clinicians. Thrombocytopenia\/ITP (also see Rheumatologic-Purpura) Purpura and ITP Feigned by quinidine ingestion- check serum quinidine level.73 Isolated thrombocytopenia has been caused by quinine ingestion.74 Infectious diseases Bacteraemia Polymicrobial bacteraemia or unusual organisms in blood cultures should raise suspicion.75,76 Case reports note stool flora, pet flora as most common exogenous material. Fever Directly observed temperature measurement using electronic thermometer. Ensure no recent ingestion of hot beverages, warm wax or wet cotton in ears. In 1979, 9% of patients presenting to an NIH study on fever of unknown origin were found to be suffering from factitious disorder.7 HIV\/AIDS Repeat HIV ELISA and Western blot, check viral load for acute HIV.77 Patient with normal CD4 count and undetectable viral load can claim suppression with anti-retrovirals. But antibody should still be positive. Wounds Apply fluorescein or tetracycline to wound, then examine hands\/nails for fluorescence. Non-healing wounds will heal when casted- but this can be circumvented by patients. Substances introduced into wounds include: human\/animal faeces, household toxins, aquarium water, foreign bodies, milk and others.78,79 Neurologic Movement disorders EMG and EEG reveal inconsistent amplitude patterns in factitious tremors and myoclonus.80 Dopaminergic drugs including antipsychotics may be taken to induce Parkinsonian symptoms. Multiple sclerosis MRI brain demonstrating at least 2 different regions of white matter change CSF with mild lymphocytosis, oligoclonal bands in IgG region. CSF protein electrophoresis is 90% sensitive in pts with active MS symptoms. Non-epileptiform seizures Serum prolactin level at baseline (near onset of epileptiform activity) then 20 minutes later.81 However this can be normal in partial-seizures and elevated in epilepsy.81 Video EEG useful but this can miss frontal lobe seizures which have movements that can suggest factitious behaviour such as pelvic thrusting and cycling movements.82,83 One estimate suggests that 15-30% of the patients presenting to epilepsy clinics with refractory epilepsy are psychogenic in nature.84 Most of these patients are unlikely to have factitious disorder. Nephrologic\/Urologic Diuretic Abuse\/Bartter syndrome Urine assays can detect furosemide, torsemide, and hydrochlorothiazide. HPLC can detect Furosemide and other diuretics.85,86 Bartter syndrome is a rare inherited defect in the ascending loop of Henle, there are at least 6 reports of factitious presentations of this condition.87 Goodpastures Syndrome See haematuria and haemoptysis sections. One patient appeared in 3 different peer reviewed articles.88-90 Haematuria Direct observation of urine collection to ensure blood or iodine not added to sample. Three tube te

Summary

Abstract

Aim

To assist clinicians in the diagnosis of factitious disorder.

Method

This is a systematic review of the role of laboratory, radiologic, procedural, and pathological modalities to assist in the diagnosis of factitious disorder (Munchausens syndrome). The review evaluated 3104 article titles and abstracts that were identified from MEDLINE as of January 2010.

Results

We found 190 articles that demonstrated techniques that will assist clinicians in recognizing fabricated manifestations of disease. The results are divided into 13 areas of clinical medicine for easy reference. They are further sub-divided by the diseases or conditions that patients have been reported to simulate and the diagnostic techniques suggested by the literature in each case.

Conclusion

Factitious disorder is difficult to diagnose and may present as a wide array of fabricated conditions, but there are a range of laboratory and technical means available to assist clinicians in the 21st Century.

Author Information

Christopher A Kenedi, Consultant, Departments of General Medicine and Liaison Psychiatry, Auckland City Hospital, Auckland, New Zealandand Adj Associate of Internal Medicine and Psychiatry, Duke University Medical Center, Durham, NC, USAand Hon Sr Lecturer. Auckland University School of Medicine, Auckland, New Zealand; Mary Hoffa, Jeremy D Harrison, Residents, Departments of Medicine and Psychiatry, Duke University Medical Center, Durham, NC, USA; Kristen G. Shirey, Joseph Zanga, Clinical Associates in Medicine and Psychiatry, Duke University Medical Center, Durham, NC, USA; Xavier A Preudhomme, Assistant Professors of Internal Medicine and Psychiatry, Duke University Medical Center, Durham, NC, USA; Jonathan C Lee, Associate Medical Director, Farley Center at Williamsburg Place, Williamsburg, VA, USA

Acknowledgements

We thank Harold Goforth MD and Jacques Wallach MD for their assistance.

Correspondence

Christopher A Kenedi, Liaison Psychiatry, Level 4 Support Building, Private Bag 92024, Auckland, 1142 New Zealand. Fax: +64 (0)9 3078945

Correspondence Email

Bluedevilkiwi-factitious@yahoo.com

Competing Interests

None.

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Factitious fever and self-induced infection: a report of 32 cases and review of the literature. Ann Intern Med. Feb 1979;90(2):230-242.Knockaert DC, Vanneste LJ, Vanneste SB, Bobbaers HJ. Fever of unknown origin in the 1980s. An update of the diagnostic spectrum. Arch Intern Med. Jan 1992;152(1):51-55.Caocci G, Pisu S, La Nasa G. A simulated case of chronic myeloid leukemia: the growing risk of Munchausen's syndrome by internet. Leuk Lymphoma. Sep 2008;49(9):1826-1828.Feldman MD. Munchausen by Internet: detecting factitious illness and crisis on the Internet. South Med J. Jul 2000;93(7):669-672.Stephenson J. Patient pretenders weave tangled \"Web\" of deceit. JAMA. Oct 21 1998;280(15):1297.Gordon LA. Watch out. Munchausen patients have found the computer. Med Econ. Sep 8 1997;74(18):118, 121, 125-117.de Fontaine S, Van Geertruyden J, Preud'homme X, Goldschmidt D. Munchausen syndrome. Ann Plast Surg. Feb 2001;46(2):153-158.Shah KA, Forman MD, Friedman HS. Munchausen's syndrome and cardiac catheterization. A case of a pernicious interaction. JAMA. Dec 10 1982;248(22):3008-3009.Krahn LE LJ, Richardson JW, Martin MJ, O'Connor MK. Hypokalemia leading to Torsades de Pointes: Munchausens disorder or bulimia nervosa? . Gen Hosp Psychiatry Sept 19 1997(5):7.Bergethon PR. Factitious ventricular tachycardia. Ann Intern Med. Oct 1987;107(4):593-594.Mitchell CC, Frank MJ. Pseudobradycardia during Holter monitoring. The electronic Munchausen syndrome? JAMA. Jul 23 1982;248(4):469-470.Burchell HB. Digitalis poisoning: historical and forensic aspects. J Am Coll Cardiol. Feb 1983;1(2 Pt 1):506-516.Chambers E, Yager J, Apfeldorf W, Camps-Romero E. Factitious aortic dissection leading to thoracotomy in a 20-year-old man. Psychosomatics. Jul-Aug 2007;48(4):355-358.Hopkins RA, Harrington CJ, Poppas A. Munchhausen Syndrome simulating acute aortic dissection. Ann Thorac Surg. Apr 2006;81(4):1497-1499.Steinwender C, Hofmann R, Kypta A, Leisch F. Recurrent symptomatic bradycardia due to secret ingestion of beta-blockers--a rare manifestation of cardiac Munchhausen syndrome. Wien Klin Wochenschr. Sep 2005;117(18):647-650.Huang J, Sun J, Zhou X, You T. Determination of atenolol and metoprolol by capillary electrophoresis with tris(2,2'-bipyridyl)ruthenium(ii) electrochemiluminescence detection. Anal Sci. Feb 2007;23(2):183-188.Flaherty ML, Infante M, Tinsley JA, Black JL, 3rd. Factitious hypertension by pseudoephedrine. Psychosomatics. Mar-Apr 2001;42(2):150-152.Fang H, Zeng Z, Liu L. Centrifuge microextraction coupled with on-line back-extraction field-amplified sample injection method for the determination of trace ephedrine derivatives in the urine and serum. Anal Chem. Sep 1 2006;78(17):6043-6049.Kailasam MT, Parmer RJ, Stone RA, et al. Factitious pheochromocytoma: novel mimickry by Valsalva maneuver and clues to diagnosis. Am J Hypertens. Jun 1995;8(6):651-655.Rude BL, Townsend RR, DiPette DJ. Case report: stimulation of severe hypertension as a means of malingering. Am J Med Sci. Oct 1992;304(4):258-260.Kwon EJ, Dans M, Koblenzer CS, Elenitsas R, James WD. Dermatitis artefacta. J Cutan Med Surg. Mar-Apr 2006;10(2):108-113.Mahirogullari M, Chloros GD, Cilli F, Cakmak S, Semiz UB, Kiral A. Factitious subcutaneous emphysema of an extremity. Joint Bone Spine. Jan 2008;75(1):84-86.Zonuz AT, Treister N, Mehdipour F, Farahani RM, Tubbs RS, Shoja MM. Factitial pemphigus-like lesions. Med Oral Patol Oral Cir Bucal. May 2007;12(3):E205-208.Rogers M, Fairley M, Santhanam R. Artefactual skin disease in children and adolescents. Australas J Dermatol. Nov 2001;42(4):264-270.Levitz SM, Tan OT. Factitious dermatosis masquerading as recurrent herpes zoster. Am J Med. Apr 1988;84(4):781-783.Lesher JL, Jr., Peterson CM, Lane JE. An unusual case of factitious onychodystrophy. Pediatr Dermatol. May-Jun 2004;21(3):239-241.Lepping P, Freudenmann RW. Delusional parasitosis: a new pathway for diagnosis and treatment. Clin Exp Dermatol. Mar 2008;33(2):113-117.Cizza G, Nieman LK, Doppman JL, et al. Factitious Cushing syndrome. J Clin Endocrinol Metab. Oct 1996;81(10):3573-3577.Lin CL, Wu TJ, Machacek DA, Jiang NS, Kao PC. Urinary free cortisol and cortisone determined by high performance liquid chromatography in the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab. Jan 1997;82(1):151-155.Mantero F, Armanini D, Opocher G, et al. Mineralocorticoid hypertension due to a nasal spray containing 9 alpha-fluoroprednisolone. Am J Med. Sep 1981;71(3):352-357.Ross DS. Syndromes of thyrotoxicosis with low radioactive iodine uptake. Endocrinol Metab Clin North Am. Mar 1998;27(1):169-185.Yoon SJ, Kim DM, Kim JU, et al. A case of thyroid storm due to thyrotoxicosis factitia. Yonsei Med J. Apr 30 2003;44(2):351-354.Gama R, Teale JD, Marks V. Best practice No 173: clinical and laboratory investigation of adult spontaneous hypoglycaemia. J Clin Pathol. Sep 2003;56(9):641-646.Earle KE, Rushakoff RJ, Goldfine ID. Inadvertent sulfonylurea overdosage and hypoglycemia in an elderly woman: failure of serum hypoglycemia screening. Diabetes Technol Ther. 2003;5(3):449-451.Horwitz DL. Factitious and artifactual hypoglycemia. Endocrinol Metab Clin North Am. Mar 1989;18(1):203-210.Baddley JW, Daberkow D, Hilton CW. Insulinoma masquerading as factitious hypoglycemia. South Med J. Nov 1998;91(11):1067-1069.Hoizey G, Lamiable D, Trenque T, et al. Identification and quantification of 8 sulfonylureas with clinical toxicology interest by liquid chromatography-ion-trap tandem mass spectrometry and library searching. Clin Chem. Sep 2005;51(9):1666-1672.Hsiao RJ, Parmer RJ, Takiyyuddin MA, O'Connor DT. Chromogranin A storage and secretion: sensitivity and specificity for the diagnosis of pheochromocytoma. Medicine (Baltimore). Jan 1991;70(1):33-45.Van Der Horst-Schrivers AN JP, Boezen HM, Schouten JP, Kema IP & Links TP. odine-123 metaiodobenzylguanidine scintigraphy in localising phaeochromocytomas--experience and meta-analysis. Anticancer Res. 2006;26:1599-1604.Stern TA, Cremens CM. Factitious pheochromocytoma. One patient history and literature review. Psychosomatics. May-Jun 1998;39(3):283-287.Portioli I, Valcavi R. Factitious phaeochromocytoma: a case for Sherlock Holmes. Br Med J (Clin Res Ed). Dec 19-26 1981;283(6307):1660-1661.Keiser HR. Surreptitious self-administration of epinephrine resulting in 'pheochromocytoma'. JAMA. Sep 18 1991;266(11):1553-1555.Topazian M, Binder HJ. Brief report: factitious diarrhea detected by measurement of stool osmolality. N Engl J Med. May 19 1994;330(20):1418-1419.Bowie EJ, Todd M, Thompson JH, Jr., Owen CA, Jr., Wright IS. Anticoagulant malingerers (the \"dicumarol-eaters\"). Am J Med. Nov 1965;39(5):855-864.Fine KD, Santa Ana CA, Fordtran JS. Diagnosis of magnesium-induced diarrhea. N Engl J Med. Apr 11 1991;324(15):1012-1017.Shelton JH, Santa Ana CA, Thompson DR, Emmett M, Fordtran JS. Factitious diarrhea induced by stimulant laxatives: accuracy of diagnosis by a clinical reference laboratory using thin layer chromatography. Clin Chem. Jan 2007;53(1):85-90.Rose MI, Dicker MA, Gouge TH. Factitious gastrointestinal bleeding: a case of autophlebotomy and ingestion. Am J Gastroenterol. Jul 1996;91(7):1457-1459.McIntyre AS, Kamm MA. A case of factitious colonic bleeding. J R Soc Med. Jul 1990;83(7):465-466.Hogenauer C, Eherer A, Pfeifer J, Langner C. Chronic longitudinal NSAID-related ulcer of the colon (\"colon single-stripe sign\") in Munchhausen syndrome. Endoscopy. Sep 2008;40 Suppl 2:E233.Klein O, Maunoury V, Cortot A, et al. Occult aspirin intake revealed by a bleeding colonic angiodysplasia. Am J Gastroenterol. Jul 1991;86(7):929-930.Bakkers JT, Crobach LF, Pauwels EK. Factitious gastrointestinal bleeding. J Nucl Med. Jun 1985;26(6):666-667.Yamashita M, Azuma J. Urinary excretion of ipecac alkaloids in human volunteers. Vet Hum Toxicol. Oct 2002;44(5):257-259.Sutphen JL, Saulsbury FT. Intentional ipecac poisoning: Munchausen syndrome by proxy. Pediatrics. Sep 1988;82(3 Pt 2):453-456.Bader AA, Kerzner B. Ipecac toxicity in \"Munchausen syndrome by proxy\". Ther Drug Monit. Apr 1999;21(2):259-260.Rashid N. Medically unexplained myopathy due to ipecac abuse. Psychosomatics. Mar-Apr 2006;47(2):167-169.Johnson JE, Carpenter BL, Benton J, Cross R, Eaton LA, Jr., Rhoads JM. Hemorrhagic colitis and pseudomelanosis coli in ipecac ingestion by proxy. J Pediatr Gastroenterol Nutr. May 1991;12(4):501-506.Johansen SS, Jensen JL. Liquid chromatography-tandem mass spectrometry determination of loperamide and its main metabolite desmethylloperamide in biological specimens and application to forensic cases. J Chromatogr B Analyt Technol Biomed Life Sci. Nov 5 2004;811(1):31-36.Schwartz JG, Xenakis EM. Munchausen's syndrome and the laboratory. Self-injection of human chorionic gonadotropin. Arch Pathol Lab Med. Jan 1995;119(1):85-88.Berry RG, Morrison JA, Watts JW, Anagnost JW, Gonzalez JJ. Surreptitious superwarfarin ingestion with brodifacoum. South Med J. Jan 2000;93(1):74-75.Chua JD, Friedenberg WR. Superwarfarin poisoning. Arch Intern Med. Sep 28 1998;158(17):1929-1932.OReilly RA AP. Covert anticoagulant ingestion: study of 25 patients and review of world literature. 1976;55(5):389-399.Schmaier AH, Carabello JA, Day HJ, Barry WE. Factitious heparin administration. Ann Intern Med. Nov 1981;95(5):592-593.Bright R, Eisendrath S, Damon L. A case of factitious aplastic anemia. Int J Psychiatry Med. 2001;31(4):433-441.Ford CV, Stein R, Kelly MP, Adelson LM. Factitial aplastic anemia. J Nerv Ment Dis. Jun 1984;172(6):369-372.Ballas SK. Factitious sickle cell acute painful episodes: a secondary type of Munchausen syndrome. Am J Hematol. Dec 1996;53(4):254-258.Ballas SK. Munchausen sickle cell painful crisis. Ann Clin Lab Sci. Jul-Aug 1992;22(4):226-228.Reid DM, Shulman NR. Drug purpura due to surreptitious quinidine intake. Ann Intern Med. Feb 1988;108(2):206-208.Abraham R, Whitehead S. Factitious quinine-induced thrombocytopenia. Med J Aust. Jan 5 1998;168(1):19-20.Catalano G, Toner LC, Alberts VA, Catalano MC. Factitious disorder presenting as bacteremia. Case report and literature review. J Fla Med Assoc. Aug 1995;82(8):535-539.Blyth CC, Russell S, Zwi KJ, Taitz J, Fairley M, Post JJ. Munchausen syndrome by proxy and recurrent polymicrobial bacteremia. Pediatr Infect Dis J. Feb 2007;26(2):191.Frumkin LR, Victoroff JI. Chronic factitious disorder with symptoms of AIDS. Am J Med. Jun 1990;88(6):694-696.Stough DB, Roberson GB, White C. A spitting image. Cutis. Feb 1989;43(2):135-136.Anderson JC, Ewan PW, Compston ND. Haemorrhage and fever in the Munchausen syndrome. Postgrad Med J. Jul 1972;48(561):445-447.Thompson PD, Colebatch JG, Brown P, et al. Voluntary stimulus-sensitive jerks and jumps mimicking myoclonus or pathological startle syndromes. Mov Disord. 1992;7(3):257-262.Trimble MR. Serum prolactin in epilepsy and hysteria. . Br Med J. 1987;2:1682-1684.Bye AM, Nunan J. Video EEG analysis of non-ictal events in children. Clin Exp Neurol. 1992;29:92-98.French J. Pseudoseizures in the era of video-electroencephalogram monitoring. Curr Opin Neurol. Apr 1995;8(2):117-120.Bodde NM, Brooks JL, Baker GA, Boon PA, Hendriksen JG, Aldenkamp AP. Psychogenic non-epileptic seizures--diagnostic issues: a critical review. Clin Neurol Neurosurg. Jan 2009;111(1):1-9.D'Avanzo M, Santinelli R, Tolone C, Bettinelli A, Bianchetti MG. Concealed administration of frusemide simulating Bartter syndrome in a 4.5-year-old boy. Pediatr Nephrol. Dec 1995;9(6):749-750.Tran HA. A woman with malaise and hyponatremia. Hyponatremia factitia (Munchausen syndrome) secondary to desmopressin use. Arch Pathol Lab Med. Feb 2006;130(2):e15-18.Sekine K, Kojima I, Fujita T, Uchino K, Isozaki S, Ogata E. Factitious Bartter's syndrome induced by surreptitious intake of furosemide. Endocrinol Jpn. Oct 1982;29(5):653-657.Duffy TP. The Red Baron. N Engl J Med. Aug 6 1992;327(6):408-411.Ifudu O, Kolasinski SL, Friedman EA. Brief report: kidney-related Munchausen's syndrome. N Engl J Med. Aug 6 1992;327(6):388-389.Flynn J. Munchausen syndrome. N Y State J Med. 1992;92:301-305.Abrol RP, Heck A, Gleckel L, Rosner F. Self-induced hematuria. J Natl Med Assoc. Feb 1990;82(2):127-128.Baker MD, Baldassano RN. Povidone iodine as a cause of factitious hematuria and abnormal urine coloration in the pediatric emergency department. Pediatr Emerg Care. Dec 1989;5(4):240-241.Fukuhara S, Kawamura N, Kakuta Y, Imazu T, Hara T, Yamaguchi S. [Case of self mutilation of urethra in a Munchausen's syndrome patient]. Hinyokika Kiyo. Nov 2007;53(11):829-831.Schmidt F, Strutz F, Quellhorst E, Muller GA. Nephrectomy and solitary kidney biopsy in a patient with Munchausen's syndrome. Nephrol Dial Transplant. May 1996;11(5):890-892.Reich JD, Hanno PM. Factitious renal colic. Urology. Dec 1997;50(6):858-862.Gault MH, Campbell NR, Aksu AE. Spurious stones. Nephron. 1988;48(4):274-279.Attar K, Lee G, Rowe E, Hudd C. The secret of the phantom stone: a case report. Int Urol Nephrol. 2004;36(1):27-28.Tojo A, Nanba S, Kimura K, et al. Factitious proteinuria in a young girl. Clin Nephrol. Jun 1990;33(6):299-302.Mitas JA, 2nd. Exogenous protein as the cause of nephrotic-range proteinuria. Am J Med. Jul 1985;79(1):115-118.Levenson JL, Chafe W, Flanagan P. Factitious ovarian cancer: feigning via resources on the internet. Psychosomatics. Jan-Feb 2007;48(1):71-73.Feldman MD, Peychers ME. Legal issues surrounding the exposure of \"Munchausen by Internet\". Psychosomatics. Sep-Oct 2007;48(5):451-452.Feldman MD. Prophylactic bilateral radical mastectomy resulting from factitious disorder. Psychosomatics. Nov-Dec 2001;42(6):519-521.Feldman MD, Hamilton JC. Mastectomy resulting from factitious disorder. Psychosomatics. Jul-Aug 2007;48(4):361.Grenga TE, Dowden RV. Munchausen's syndrome and prophylactic mastectomy. Plast Reconstr Surg. Jul 1987;80(1):119-120.Rosenberg MW, Hughes LE. Artefactual breast disease: a report of three cases. Br J Surg. Jul 1985;72(7):539-541.Warrens AN, Ron MA, Dawling S. Positive diagnosis of self-medication with homatropine eye drops. Br J Psychiatry. Jan 1990;156:124-125.Rosenberg PN, Krohel GB, Webb RM, Hepler RS. Ocular Munchausen's syndrome. Ophthalmology. Aug 1986;93(8):1120-1123.Lembach RG, Ringel DM. Factitious bilateral crystalline keratopathy. Cornea. Jul 1990;9(3):246-248.Minemura K, Nagahara M, Kaburaki T, et al. [Case of recurrent fungal endophthalmitis with suspected Munchausen syndrome]. Nippon Ganka Gakkai Zasshi. Mar 2006;110(3):188-192.Mushtaq B, Kumar V, Saeed T, Bacon PA, Murray PI. Self-inflicted anterior scleritis. Eye. Jan 2003;17(1):107-108.Zamir E, Read RW, Rao NA. Self-inflicted anterior scleritis. Ophthalmology. Jan 2001;108(1):192-195.Pokroy R, Marcovich A. Self-inflicted (factitious) conjunctivitis. Ophthalmology. Apr 2003;110(4):790-795.Baskin DE, Stein F, Coats DK, Paysse EA. Recurrent conjunctivitis as a presentation of munchausen syndrome by proxy. Ophthalmology. Aug 2003;110(8):1582-1584.Kapoor HK, Jaison SG, Chopra R, Kakkar N. Factitious keratoconjunctivitis. Indian J Ophthalmol. Dec 2006;54(4):282-283.Vaiman M, Shoval G, Gavriel H. The electrodiagnostic examination of psychogenic swallowing disorders. Eur Arch Otorhinolaryngol. Jun 2008;265(6):663-668.Egan AJ, Tazelaar HD, Myers JL, Abell-Aleff PC. Munchausen syndrome presenting as pulmonary talcosis. Arch Pathol Lab Med. Aug 1999;123(8):736-738.Hendrix S, Sale S, Zeiss CR, Utley J, Patterson R. Factitious Hymenoptera allergic emergency: a report of a new variant of Munchausen's syndrome. J Allergy Clin Immunol. Jan 1981;67(1):8-13.Patterson R, Schatz M. Factitious allergic emergencies: anaphylaxis and laryngeal \"edema\". J Allergy Clin Immunol. Aug 1975;56(2):152-159.Croft PR, Racz MI, Bloch JD, Palmer CH. Autopsy confirmation of severe pulmonary interstitial fibrosis secondary to Munchausen syndrome presenting as cystic fibrosis. J Forensic Sci. Sep 2005;50(5):1194-1198.Leonard A, Leal T, Godding V, Villanueva P, Wallemacq P, Lebecque P. Sweat potassium concentration may help to identify falsification of sweat test: a case report. Clin Biochem. Sep 2008;41(13):1110-1112.Rusakow LS, Gershan WM. Hemoptysis and Munchausen syndrome. Chest. Oct 1994;106(4):1308-1309.Kokturk N, Ekim N, Aslan S, Kanbay A, Acar AT. A rare cause of hemoptysis: factitious disorder. South Med J. Feb 2006;99(2):186-187.Baktari JB, Tashkin DP, Small GW. Factitious hemoptysis. Adding to the differential diagnosis. Chest. Mar 1994;105(3):943-945.Burkle FM, Jr., Calabro JJ, Parks FB. Munchausen's syndrome presenting as respiratory failure requiring intubation. Ann Emerg Med. Feb 1987;16(2):203-208.Cole RP, Walter KL. Factitious intrinsic PEEP in a patient with respiratory failure. Respiration. 2001;68(5):555.Klaassen FA, Schober P, Schwarte LA, Boer C, Loer SA. Acute respiratory failure leading to emergency intubation: an unusual manifestation of Munchausen's syndrome. Resuscitation. Dec 2007;75(3):534-539.Samaniah N, Horowitz J, Buskila D, Sukenik S. An unusual case of factitious arthritis. J Rheumatol. Sep 1991;18(9):1424-1426.Apfelbaum JD, Williams HJ. Factitious simulation of systemic lupus erythematosus. West J Med. Mar 1994;160(3):259-261.Fonseca E, Rubio G. Factitious systemic lupus erythematosus. Lupus. Jun 1993;2(3):195-197.Archer-Dubon C, Orozco-Topete R, Reyes-Gutierrez E. Two cases of psychogenic purpura. Rev Invest Clin. Mar-Apr 1998;50(2):145-148.

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Patients with factitious disorder seek to be cared for despite the lack of an underlying illness. To obtain "the sick role" they fake symptoms, fabricate history and manipulate their bodies and medical investigations to simulate a condition that will require medical or surgical care. Unlike patients who are seeking a reward—e.g. workman's compensation, or narcotics, their goal is solely to receive emotional support and medical attention.Despite the passage of 60 years since Asher first described factitious behaviour and labelled it Munchausen's syndrome, the accurate diagnosis of factitious disorder is still as challenging for clinicians today as it was in 1951.1 As a psychiatric condition that is usually seen by non-psychiatrists, it is under-recognized and under-appreciated in terms of its contribution to unnecessary morbidity and mortality as well as the cost to healthcare systems.Factitious disorder is usually first suspected when inexplicable laboratory results are noted in the course of a prolonged clinical investigation.2 Therefore, it is essential that clinicians be aware of the state-of-the-art techniques available to diagnose illness fabrication in the context of factitious disorder. Figure 1. Diagnostic criteria DSM-IV Diagnostic criteria for factitious disorder Intentional production or feigning of physical or psychological signs or symptoms. The motivation for the behaviour is to assume the sick role. External incentives for the behaviour (such as economic gain, avoiding legal responsibility, or improving physical well-being, as in Malingering) are absent. Surveys demonstrate that physicians across medical specialties are uncomfortable with diagnosing factitious disorder.3 Estimates of the incidence of factitious disorder among general hospital admissions range from 0.6% to 1.3%.3-5 Another report indicated that 3% of non-psychiatric hospital admissions over an 8-year period were by patients who had no known organic basis for their complaint.6 Other studies looking at specific problems such as fever of unknown origin have found a factitious basis for 3.5%-9.3% of cases.7,8 These numbers presumably represent a fraction of the cases that actually occur, since they do not include those who are not suspected or never detected. Factitious disorder not only impacts the doctor-patient relationship, it also results in a financial burden on the healthcare system. From case reports, we know patients with factitious disorder often undergo lengthy hospital stays and numerous tests and procedures before their activities are recognised. With advances in technology, there is both an increase in our diagnostic armamentarium as well as a greater expectation that we will obtain a diagnosis in a rapid fashion. Because factitious presentations will not make sense in a traditional medical context—wounds that do not heal, diarrhoea without an apparent cause, blood sugars that continue to be low despite treatment—most clinicians will assume that they are missing the diagnosis and pursue increasingly obscure (and often expensive or invasive) workups. Methods Definitions Eligibility criteria for inclusion in the systematic review: Studies of patients who fabricated illness, where their fabrication was detected by the use of laboratory or technical means. Technical means—This included any laboratory or procedural test that could be ordered from a hospital laboratory or a reference laboratory, or a reproducible test that involved technology or equipment that should be available at an academic medical centre through medical, neurological, surgical or pathology specialty and sub-specialty services in the first world. Factitious disorder—For the purposes of this review, a patient with factitious disorder is defined as a person who intentionally feigns or manufactures symptoms or signs of disease for the purposes of obtaining medical care and without other external motives for their behaviour. We intentionally exclude other conditions such as malingering, conversion disorder, hypochondriasis, noncompliance, suicidal acts, admitted self-harm behaviours, iatrogenic misadventures, and errors by laboratories or mistakes of interpretation by clinicians. The authors performed a systemic review of the literature to evaluate laboratory and technical methods that can assist diagnosticians in recognizing factitious disorder. We evaluated a possible 3104 citations to develop a state of the art guide for clinicians to use in diagnosing factitious disorder. The focus of our review was solely on the use of laboratory and technical methods (including the use of radiology, endoscopy, neurodiagnostic tools, and histology, among other modalities) to recognize when patients may have manipulated their clinical presentation to assume the sick role. Primary search string—((Factitious - (as MeSH term and Keyword)) OR (Munchhausen) OR (Munchausen—(as MeSH term and Keyword)) OR (fantastica) OR (dermatitis artefacta)). The search was current through January 2010. Note that adding the MeSH term or keyword of "somatoform" increases the yield to 9763 articles but did not appear to offer any advantage when this search was further developed or subcategories were added. "Psychogenic" was an exception to search terms as it did bring additional cases and reports to light, but only in the field of neurology where it is applied to non-epileptic seizures and to movement disorders without an identified organic basis. Additional searches were performed using variants of: autodestructive, somatic, somatisation, hypochondr*, faking, fabricated, faked, fictitious, artefacta, pseudologia, Asher, Ganser's, "by proxy." However none of these search strings as keywords (or MESH terms) resulted in additional relevant articles. Three articles were found in the cited bibliographies of papers on factitious disorder that were not found in literature searches. Databases reviewed—This search string in Medline (PubMed) resulted in 3104 articles. 1088 involved primary reports of factitious manifestations of specific disorders. 190 of these articles offered unique and applicable information. An additional search in PsyINFO did not offer any articles that addressed novel issues of clinical diagnostic methodology. We also consulted with multiple specialists from each medical and surgical specialty - at several major medical centres in the United States and New Zealand - for additional examples of useful tests not covered in the literature, but none were suggested. The European literature database EMBASE was also reviewed but not systematically. No additional articles were found using checks of above terminology. Articles without English abstracts were not investigated if their title did not appear to be directly relevant. A conscious decision was made not to survey the forensic pathology or biochemistry literature for discussions of techniques not previously applied to factitious disorder. This was done to limit the review to articles of significance to practicing clinicians, most of whom will not have access to specialized laboratories services. In general, the tests discussed should be available at an academic medical centre, reference laboratory or through normal consultation with medical and surgical specialists and clinical pathologists. Results The table below represents the information gained from the 190 articles that offered methods for the diagnosis of factitious disorder. Table 1. Tools for diagnosing factitious disorder by speciality and condition SYMPTOM LABORATORY TEST COMMENTS Cardiovascular Angina Definitive test: coronary angiography. Also consider: stress test, ECG, Echocardiogram for wall motion abnormalities.14 History of prior myocardial infarction or cardiac bypass does NOT exclude factitious presentation- may represent the patient fabricating prior symptoms. Arrhythmia Consider indirect dysrhythmia though manipulated electrolytes (Mg, K).15Supervise telemetry lead placement to avoid manipulation.16,17 Digitalis, beta-blockers and calcium channel blockers can be measured in serum.18 Arrhythmias have also been reported in patients with surreptitious laxative or thyroxine abuse (see below). Aortic dissection In patients reportedly unable to receive CT aortogram with contrast or MRI, consider transthoracic echocardiogram.19,20 Patient's goal may be thoracotomy. Patients have reported an allergy to radiography contrast prohibiting CT imaging. Also allergy to gadolinium or shrapnel residue in their body prohibiting MRI. Hypotension Serum assays for beta-blockers and calcium channel blockers. Electrochemiluminescence assays detect atenolol and metoprolol in urine samples.21,22 Capillary electrophoresis with electrochemiluminescence detection - assays developed to detect doping in sports. Hypertension Serum or urine assay for pseudoephedrine.23,24pheochromocytoma can also be simulated.25,26 Valsalva manoeuvre may be used by the patient during BP measurement to produce transient HTN. Dermatologic Chelitis granulomatosa Liver and lymph node biopsies may show histiocytes that contain Polyvinylpyrrolidone (PVP) suggesting self-inoculation. PVP, a polymer, is used in hair sprays, skin care products, fruit juices, Dermatitis artefacta, chelitis, Subcutaneous emphysema Punch biopsy with histopathology- may reveal evidence of mechanical trauma with areas of necrosis and extravasation of RBCs.27 Imaging or skin exam can note needle tracks for subcutaneous air.28 Erythematous lesion, pemphigus Apply alcohol to lesion.29,30 Direct immunofluorescence.29 Herpes Zoster Negative viral PCR.31 Onychodystrophy Microscopy.32 Nail file to replicate symptoms. Scabies Scabies PCR, microscopy.33 Endocrine Cushing's syndrome High-pressure liquid chromatography (HPLC) used to distinguish exogenous vs. endogenous glucocorticoids.34Cortisol and corticosterone are co-secreted, so both should be checked since corticosterone will not be elevated if cortisol is surreptitiously added to urine samples.35 Surreptitious addition of hydrocortisone requires measurement of upstream metabolites to check for evidence of suppressed pituitary secretion of ACTH. Hyperaldosteronism Glycyrrhizic acid can be detected in serum.36 The ingestion of black liquorice has gained particular notoriety on the internet. The sweetener used to make licorice, glycyrrhizic acid can lead to treatment-resistant hypokalemia, metabolic alkalosis and hypernatremia. Hyperthyroidism TSH, T3, free T4, thyroglobulin, and thyroid autoantibody. Some recommend 24h radioiodine uptake testing.37 During thyroid storm factitious hyperthyroidism is the only aetiology in which TSH will be low.38 Some herbal medications contain thyroid hormones. Serum thyroglobulin may less useful as 10-20% of people have anti-thyroglobulin antibodies that may affect thyroglobulin measurement. Hypoglycaemia Serum insulin, C-peptide, and proinsulin levels, assays for metformin, meglitinides, sulfonylureas.39 Novel incretin analogue exenatide and amylin analogue pramlintide not routinely included in hypoglycaemic drug screens.40 Also consider manipulation of testing strips.41 Urine can be more sensitive than serum and may remain positive for a longer period.42,43 Anti-insulin antibodies no longer useful as more human recombinant insulin is used. Also C-peptide is cleared renally and will be elevated in renal failure. Pheochromocytoma Serum chromogranin A useful to identify true pheochromocytoma. 44 Meta-iodobenzylguanidine (nuclear scan is probably the gold standard.45Vanillylmandelic acid (VMA) should not be used for suspected factitious pheochromocytoma because vanilla extract or foods high in vanillin can elevate VMA.46 Agents to mimic pheochromocytoma symptoms include self-administration of epinephrine, metaraminol, and isoproternol.47,48 patients can use the Valsalva manoeuvre to produce a symptom pattern suggestive of pheochromocytoma.25,26 Gastrointestinal Diarrhoea Surreptitious addition of water to stools detected by measuring faecal fluid osmolality - if less than 290 mosm\/kg, water or hypotonic solution may have been added to stool.49Consider 3-day stool collection for 200g\/day volume check.50,51 Urine screen for phenolphthaleins, anthraquinones, and bisacodyl plus stool screen for magnesium and phosphate.52 Urine and stool "laxative abuse" screens often need to be performed multiple times due to intermittent laxative use by patients and low sensitivity of the tests. Gastrointestinal (GI) bleeding Factitious bleeding suggested when nasogastric tube shows blood but no cause found on oesophagogastroduodeno-scopy.53Colonoscopy is less sensitive to elucidate lower GI bleeding.54 The "single-stripe" sign on colonoscopy may indicate non-steroidal anti-inflammatory abuse, which can be detected on high performance liquid chromatography (HPLC).55 Ingestion of salicylates can also cause factitious lower GI bleeds.56Radiolabelling only useful in a patient injecting themselves with blood they had obtained from transfusions in-hospital; discovered when rectal blood was found not to be radiolabelled after a radio-isotope injection.57 Nausea\/vomiting When produced by ipecac consumption, measure serum or urine emetine levels (detectable by HPLC).58Elevated creatine kinase, leukocytosis, and transaminitis also associated with ipecac toxicity.59 After vomiting episodes, clinicians should see low serum potassium, low chloride after acute vomiting or prolonged episodes of vomiting. Excess ipecac induces myopathic toxicity including skeletal muscle weakness and hypotonia and cardiomyopathy with dysrhythmias, T-wave abnormalities, and prolonged QT interval.60-62 Pseudo-obstruction Detect loperamide or another motility slowing agent by HPLC of blood or stool.63 Gynaecology and Obstetrics False Ectopic Pregnancy Self-injection of human chorionic gonadotropin (hCG) has been reported. This led to a negative urine beta-hCG and negative ultrasound. Also subsequent serum beta-hCG levels were widely varying.64 Vaginal Discharge Typically the fluids have an inconsistent pH or the vaginal wall shows evidence of trauma\/abrasion in patients denying intercourse or instrumentation. Hematologic Anaemia\/Bleeding Examination may show evidence of venipuncture or instrumentation, particularly of orifices or the genital-urinary tract or gastrointestinal tract on endoscopy.1 Anticoagulation For patients not known to be on warfarin, administer vitamin K, and then re-check PT\/INR. Warfarin can be assayed directly but warfarin derivatives such as the rodenticide brodifacoum require use of HPLC.65,66 For patients on warfarin, there can be "false-resistance" to warfarin that requires extensive clinical input and attention. This must be cautiously approached as genetics can play a large role. If vitamin K and plasma Warfarin levels are irregular, consider genetic testing if there is no indication of factitious behaviour.67 Prolonged PTT but normal reptilase time suggest presence of heparin. Another test is to add protamine sulphate or an ion-exchange resin to the blood sample which will indicate the presence of exogenous heparin.68 The most common hematologic factitious disorder is surreptitious anticoagulation abuse. Aplastic Anaemia This has been provoked by the ingestion of alkylating agents such as busulfan or other chemotherapy agents.69,70 Sickle Cell Disease Confirmation with haemoglobin electrophoresis.71,72 Important for patients not known to local clinicians. Thrombocytopenia\/ITP (also see Rheumatologic-Purpura) Purpura and ITP Feigned by quinidine ingestion- check serum quinidine level.73 Isolated thrombocytopenia has been caused by quinine ingestion.74 Infectious diseases Bacteraemia Polymicrobial bacteraemia or unusual organisms in blood cultures should raise suspicion.75,76 Case reports note stool flora, pet flora as most common exogenous material. Fever Directly observed temperature measurement using electronic thermometer. Ensure no recent ingestion of hot beverages, warm wax or wet cotton in ears. In 1979, 9% of patients presenting to an NIH study on fever of unknown origin were found to be suffering from factitious disorder.7 HIV\/AIDS Repeat HIV ELISA and Western blot, check viral load for acute HIV.77 Patient with normal CD4 count and undetectable viral load can claim suppression with anti-retrovirals. But antibody should still be positive. Wounds Apply fluorescein or tetracycline to wound, then examine hands\/nails for fluorescence. Non-healing wounds will heal when casted- but this can be circumvented by patients. Substances introduced into wounds include: human\/animal faeces, household toxins, aquarium water, foreign bodies, milk and others.78,79 Neurologic Movement disorders EMG and EEG reveal inconsistent amplitude patterns in factitious tremors and myoclonus.80 Dopaminergic drugs including antipsychotics may be taken to induce Parkinsonian symptoms. Multiple sclerosis MRI brain demonstrating at least 2 different regions of white matter change CSF with mild lymphocytosis, oligoclonal bands in IgG region. CSF protein electrophoresis is 90% sensitive in pts with active MS symptoms. Non-epileptiform seizures Serum prolactin level at baseline (near onset of epileptiform activity) then 20 minutes later.81 However this can be normal in partial-seizures and elevated in epilepsy.81 Video EEG useful but this can miss frontal lobe seizures which have movements that can suggest factitious behaviour such as pelvic thrusting and cycling movements.82,83 One estimate suggests that 15-30% of the patients presenting to epilepsy clinics with refractory epilepsy are psychogenic in nature.84 Most of these patients are unlikely to have factitious disorder. Nephrologic\/Urologic Diuretic Abuse\/Bartter syndrome Urine assays can detect furosemide, torsemide, and hydrochlorothiazide. HPLC can detect Furosemide and other diuretics.85,86 Bartter syndrome is a rare inherited defect in the ascending loop of Henle, there are at least 6 reports of factitious presentations of this condition.87 Goodpastures Syndrome See haematuria and haemoptysis sections. One patient appeared in 3 different peer reviewed articles.88-90 Haematuria Direct observation of urine collection to ensure blood or iodine not added to sample. Three tube te

Summary

Abstract

Aim

To assist clinicians in the diagnosis of factitious disorder.

Method

This is a systematic review of the role of laboratory, radiologic, procedural, and pathological modalities to assist in the diagnosis of factitious disorder (Munchausens syndrome). The review evaluated 3104 article titles and abstracts that were identified from MEDLINE as of January 2010.

Results

We found 190 articles that demonstrated techniques that will assist clinicians in recognizing fabricated manifestations of disease. The results are divided into 13 areas of clinical medicine for easy reference. They are further sub-divided by the diseases or conditions that patients have been reported to simulate and the diagnostic techniques suggested by the literature in each case.

Conclusion

Factitious disorder is difficult to diagnose and may present as a wide array of fabricated conditions, but there are a range of laboratory and technical means available to assist clinicians in the 21st Century.

Author Information

Christopher A Kenedi, Consultant, Departments of General Medicine and Liaison Psychiatry, Auckland City Hospital, Auckland, New Zealandand Adj Associate of Internal Medicine and Psychiatry, Duke University Medical Center, Durham, NC, USAand Hon Sr Lecturer. Auckland University School of Medicine, Auckland, New Zealand; Mary Hoffa, Jeremy D Harrison, Residents, Departments of Medicine and Psychiatry, Duke University Medical Center, Durham, NC, USA; Kristen G. Shirey, Joseph Zanga, Clinical Associates in Medicine and Psychiatry, Duke University Medical Center, Durham, NC, USA; Xavier A Preudhomme, Assistant Professors of Internal Medicine and Psychiatry, Duke University Medical Center, Durham, NC, USA; Jonathan C Lee, Associate Medical Director, Farley Center at Williamsburg Place, Williamsburg, VA, USA

Acknowledgements

We thank Harold Goforth MD and Jacques Wallach MD for their assistance.

Correspondence

Christopher A Kenedi, Liaison Psychiatry, Level 4 Support Building, Private Bag 92024, Auckland, 1142 New Zealand. Fax: +64 (0)9 3078945

Correspondence Email

Bluedevilkiwi-factitious@yahoo.com

Competing Interests

None.

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