Acute Intermittent Porphyria Presenting Solely with Psychosis: A Case Report and Discussion

Psychosomatics 2012:53:494 – 498

© 2012 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Case Reports Acute Intermittent Porphyria Presenting Solely with Psychosis: A Case Report and Discussion Bharat Kumar, M.D.

A

cute intermittent porphyria (AIP) is caused by an inborn error of heme metabolism; it is characterized by the accumulation of neurotoxic heme intermediates, particularly aminolevulinic acid (ALA) and porphobilogen (PBG).1 Though classically described as a triad of abdominal pain, peripheral neuropathy, and neuropsychiatric disturbance, AIP has been known to present in a multitude of ways with both psychiatric and somatic complaints.2 Here we present a case of an acute porphyric attack manifesting exclusively as psychosis without any accompanying somatic features. We further review the neuropsychiatric manifestations of the disease and detail the importance of obtaining a comprehensive history and physical examination in order to identify the psychosomatic manifestations of this puzzling disease.

Case Report

Ms. B, a 15-year-old African-American female diagnosed with schizophrenia approximately 1 year ago presented to the psychiatric hospital with bizarre behavior of 2 days’ duration. Her speech was loose and tangential, thought process nonlinear, and thought content marked by paranoid claims that her classmates were extraterrestrials planning to take advantage of her. As relayed by her mother and her schoolteacher, prior to this episode, she was performing well in school and was socially active in numerous activities. Ms. B was noted to have been hospitalized 9 months prior for similar symptoms, where she was administered high doses of risperidone and quetiapine. After 5 days, she was discharged with follow-up from an outpatient psychiatrist who tapered down and ultimately discontinued risperidone and quetiapine. Her mother also explained that she has had 3 minor episodes after the initial hospitalization, where she was “talking and acting funny” but that her 494

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behavior was not of enough concern to take her to the hospital. On further questioning, her mother also disclosed that these episodes tended to be preceded by small “head colds.” There was no family history of mental illness. On admission, her pulse was 92 beats/minute, her blood pressure was 130/80 mmHg, her respiratory rate was 24 beats/minute, and her temperature was 98.4°C. Her speech was loose and tangential, and her thought process disorganized. Ms. B was administered haloperidol 10 mg po QID, and quetiapine 100 mg po qAM. The physical examination revealed congestion and erythema in the throat. Abdominal and neurological examinations were normal. Urine toxicology screen was negative although the urine was noted to be amber-colored. Basic metabolic panel was within normal limits. Complete blood count demonstrated mild leukocytosis (11.0 cells/mm) with predominance of neutrophils (65.6%). Due to the presence of leukocytosis, the history of psychotic symptoms following minor infection, and the drug-resistant nature of her illness, the previous diagnosis of schizophrenia was reassessed, and psychosis due to a general medical condition was considered. In particular, Ms. B’s amber-colored urine and history of antecedent upper respiratory tract infections increased suspicion of an acute porphyric attack. Elevated delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels were found in urine collected over 24 hours (15.70 mg [normal: 0 –5 mg] and 6.4 mg [normal: 0 –2 mg], respectively), thus establishing the diReceived March 13, 2012; revised March 26, 2012; accepted March 27, 2012. From Department of Internal Medicine, University of Kentucky Chandler Medical Center, Lexington, KY 40536. Send correspondence and reprint requests to Bharat Kumar, M.D., Department of Internal Medicine, University of Kentucky Chandler Medical Center, J525 Kentucky Clinic, 740 South Limestone St., Lexington, KY 40536; e-mail: [email protected] © 2012 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

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Kumar agnosis of acute intermittent porphyria. All porphyrogenic medications, including haloperidol and quetiapine, were immediately discontinued, and chlorpromazine was started. Ms. B was then treated symptomatically. After 3 days of hospitalization, she slowly returned to her level of functioning prior to this episode. Twelve months following hospitalization, Ms. B continued to do well in school and in her extracurricular activities. She maintained regular appointments with her hematologist and psychiatrist, both of whom discussed strategies to avoid triggers for porphyric attacks, including oral contraception, abstention from alcohol, and a high carbohydrate diet. Her immediate family members were also offered testing for the condition, but they declined.

Discussion

AIP is caused by an inborn error of heme metabolism characterized by deficient activity of the enzyme porphobilinogen deaminase (PGBD), and accumulation of its substrates, porphobilinogen (PBG) and delta-aminolevulinic acid (ALA).1 Though transmitted in an autosomal dominant manner, the course of the illness is typically indolent with only 10% ever experiencing an acute porphyric episode.3 For this reason, epidemiologists have been unable to accurately determine the prevalence of the disease, though studies have suggested that 0.01% of the general population, and 0.21%– 0.45% of the psychiatric population have increased levels of PBG in their urine, predisposing them to acute porphyric attacks.4 When symptomatic, patients with elevated porphyrin levels often complain of a number of vague and seemingly unrelated complaints. Due to this chimeric nature of the disease, along with its rarity in most populations, acute porphyric attacks are often overlooked by clinicians and consequently misdiagnosed.5 At the same time, since diagnostic tests for porphyria are expensive and technically challenging, the physician must be judicious in deciding whether porphyria is a likely diagnosis.1,2,6 Therefore, a high index of clinical suspicion informed by a detailed history and physical examination is absolutely necessary for the timely diagnosis of AIP. Classically, AIP has been described as a triad of abdominal pain, peripheral neuropathy, and mental status changes. Additionally, autonomic instability and electrolyte disturbances, particularly hyponatremia, are cited to be quite common.1,2 Among these, the most characteristic symptom, seen in 90% of patients, is a severe, diffuse abdominal pain, often Psychosomatics 53:5, September-October 2012

associated with changes in bowel movements.5 Peripheral neuropathies secondary to axonal degeneration are also wellcharacterized, occurring in 20% of patients and manifesting with proximal muscle weakness, diminution of reflexes, and dysesthesias.7 Because the abdominal examination is typically fairly benign and neurological deficits occur in a seemingly haphazard fashion, diagnosis of AIP is often discounted in favor of a factitious illness or somatoform disorder.8,9 The third aspect of the triad, neuropsychiatric symptoms, poses a particularly challenging dilemma for clinicians. As many as 19% to 58% of patients exhibit at least one neuropsychiatric disturbance.2 On cursory examination, these symptoms may be ascribed to more common psychiatric illnesses, such as anxiety, depression, insomnia, or a psychotic disorder.3,8 However, the context and character of these symptoms are often distinct from their organic counterparts; unlike primary mental illness, these symptoms can often be distinguished by their strong temporal correlation to antecedent triggers and often remitting and relapsing patterns.10 Though rare, several cases of AIP have been documented in which the presentation has been predominantly psychiatric in nature. Indeed, a detailed MEDLINE literature search (Figure 1) reveals 19 other cases in which neuropsychiatric symptoms were the main features of an attack. Given this chimeric nature of AIP, physicians ought to maintain a high threshold of clinical suspicion and obtain a detailed history and physical examination to aggressively rule out an acute porphyric attack. On examination, subtle findings may suggest a diagnosis. In our case, the strong temporal relationship between Ms. B’s upper respiratory tract infections and her episodes of psychosis seemed to suggest an organic cause of disease. Indeed, porphyric attacks are commonly presaged by environmental triggers, which lead to the up-regulation of the heme synthesis pathway and the subsequent accumulation of porphyrins.2,3 Aside from infection, other leading triggers of acute porphyric attacks include menstruation, excessive alcohol consumption, smoking, fasting, prescription drugs, and emotional stress.10 In retrospect, the initial diagnosis of schizophrenia seemed to be the result of premature closure and underscored the necessity of aggressive medical investigation prior to establishment of a psychiatric diagnosis. Indeed, the acute onset of symptoms, lack of discernible prodrome, and resistance to multiple antipsychotic medications seemed at odds with the established diagnosis, www.psychosomaticsjournal.org

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Case Reports

FIGURE 1.

Reported Cases of AIP Presenting Predominantly with Psychiatric Complaints. Cases refer to references2,3,8,10,12,14 –20 Reported Case *

Psychiatric Complaint

Soma
c Manifesta
on

Floru,14 1974

Paranoid delusions

Abdominal pain

Carter,10 1977

Self-mu
la
on

Abdominal pain, increasing paralysis

Grabowsky et al,15 1987

Chronic psycho
c illness

Asymmetric neuropathic lesions

Santosh et al,8 1994

Delirium, catatonic stupor, hypomania, muteness

Fever, abdominal pain

Crimlisk et al,2 1997

Emo
onal lability, agita
on, ideas of reference, auditory hallucina
ons

Abdominal pain

Regan et al,3 1999

Anxiety, depressed mood

Progressive motor weakness

Narang et al,16 2003

Hallucina
ons, disorienta
on

Febrile, autonomic instability

Narang et al,16 2003

Paranoid delusions

Autonomic instability

Narang et al,16 2003

Visual hallucina
ons, inappropriate affect, psychomotor retarda
on

Abnormal nerve conduc
on study

Ellencweig et al,17 2006

Psychosis, agita
on

“Mild hypertension of unknown e
ology”

Zimmerman et al,18 2006

Acute mental changes, hallucina
ons

Subacute tetraparesis, abdominal pain

Ghosh et al,19 2006

Poor sleep, crying spells, obsessive rumina
on, pseudoauditory hallucina
on, depression

Cons
pa
on,
ngling of limbs, generalized tonic-clonic seizures, paralysis, semi-stupor

Ghosh et al,19 2006

Uncoopera
ve behavior, delirium

Peripheral neuropathy, generalized tonic-clonic seizures, CN IX & X palsy

Ghosh et al,19 2006

Sleeplessness, irritability, aggression

Episodic abdominal pain, paroxysmal tachycardia

Ghosh et al,19 2006

Delusions, psychosis

Abdominal pain, cons
pa
on

Ghosh et al,19 2006

Loss of consciousness, giddiness, anxiety, depression

Atonic seizures, autonomic lability, abdominal pain

Ghosh et al,19 2006

Forgeulness, sleeplessness, deteriora
on in social func
oning

Generalized tonic-clonic seizures

Al
ntoprak et al,20 2009

Paranoid delusions, visual and auditory hallucina
ons

“Stocking and glove” paraesthesias

Menegue
et al,12 2011

Visual hallucina
ons

Pain in lower extremi
es and abdomen

*Cases found through MEDLINE search terms “Acute Intermient Porphyria,” “Acute Porphyric Aack,” “AIP,” “Hepa
c Porphyria,” “Psychosis,” “Psychiatric,” “Neuropsychiatric,” “Anxiety,” “Depression,” “Hallucina
ons,” “Delusions,” “Schizophrenia,” “Insomnia,” and “Mental illness.”

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Psychosomatics 53:5, September-October 2012

Kumar and prompted a thorough re-evaluation of Ms. B’s condition. In patients with a suggestive history and physical examination, the measurement of urine or serum PBG and ALA over 24 hours may confirm the diagnosis.11 Grossly high levels of PBG may discolor the urine, leading to an amber or ‘port wine’ colored urine that fluoresces under ultraviolet light.6 During acute attacks, levels are often greatly elevated, though less dramatic elevations are nonspecific and may also be seen in latent AIP and other conditions.6,11 In equivocal cases, diagnosis can be further confirmed through red cell PBGD activity, or DNA testing, though the latter is not routinely performed.6 Though the mainstay of treatment is symptomatic and supportive, establishment of the diagnosis of AIP is essential to proper management as many common medications are porphyrogenic and may be ineffective or exacerbate the condition further. Suitable alternatives to neuroleptic agents should be sought, such as amitriptyline, imipramine, and phenothiazines.1,2 Opiates may be safely administered for pain relief while propranolol may be used to treat sympathetic overactivity.1,2,12 Finally, in more advanced cases, hemin and other heme oxygenase inhibitors (i.e., tin and zinc metalloporphyrins) may be administered to reduce the synthesis of PBG and ALA.13 Once the porphyric attack has subsided, the patient should be counseled on strategies to prevent future episodes. Abstaining from alcohol, maintenance of a high

carbohydrate diet, and hormonal regulation via oral contraception pills are lifestyle changes that can help to prevent subsequent life-threatening crises.1,2,10 Finally, immediate family members should be tested to identify carriers who may also be at risk for this condition.2,6,11

Conclusion

AIP is a rare but important metabolic disease with psychosomatic components, the diagnosis of which is often delayed or missed altogether due to its rarity and the variable nature of presentation. Though it has long been thought of as a somatic disease with psychiatric overtones, as this case demonstrates, the lack of somatic complaints, such as abdominal pain or neuropathy does not sufficiently exclude a diagnosis. Therefore, the physician ought to maintain a high level of clinical suspicion and aggressively rule out the diagnosis in patients with suggestive historical findings, such as the coincidence of psychiatric disease with new drugs or infection, as well as a lack of response to standard, often porphyrogenic, medications. Early establishment of a diagnosis enables effective treatment that may reduce permanent neuropsychiatric sequelae and guide treatment in subsequent episodes. Disclosure: The author disclosed no proprietary or commercial interest in any product mentioned or concept discussed in this article.

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18. Zimmermann M, Bonaccurso C, Valerius C, Hamann GF: [Acute intermittent porphyria. A clinical chameleon: case study of a 40year-old female patient]. Nervenarzt 2006; 77(12):1501–1505 19. Ghosh S, Chaudhary P, Goswami H: An analysis of six cases of acute intermittent porphyria (AIP). Indian J Psychiatry 2006; 48(3):189 –192 20. Altintoprak AE, Ersel M, Bayrakci A: An unusual suicide attempt: a case with psychosis during an acute porphyric attack. Eur J Emerg Med 2009; 16(2):106 –108

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