Rev Bras Anestesiol
2010; 60: 6: 634-638
CLINICAL INFORMATION
Neuropathic Pain in a Patient with Porphyria.
Case Report
Alysson B. O. Santos 1, Judymara L. Gozzani, TSA 2, Daniela F. Groke 3
Summary: Santos ABO, Gozzani JL, Groke DF – Neuropathic Pain in a Patient with Porphyria. Case Report.
Background and objectives: Porphyrias represent a group of inherited or acquired disorders that involve enzymes that participate in heme synthesis. Acute manifestations affect the nervous system resulting in abdominal pain, vomiting, acute neuropathy, seizures, and mental disorders.
The physiopathogeny results from the toxic effects of porphyrin precursors, and it can be triggered by drugs used routinely in medical practice,
severe carbohydrate restriction, and metabolic stress. The objective of this report was to present the case of a late onset porphyria evolving to
chronic pain.
Case report: This is a 27 years old female who was admitted 5 months prior to her clinic appointment with severe abdominal pain without diagnosis. An exploratory laparotomy was indicated, which failed to demonstrate a cause for her pain. The patient was exposed to surgical trauma and
drugs that can trigger porphyria, such as ketoprophen, metoclopramide, and antibiotics, and she evolved with significant hyponatremia, increased
liver enzymes, seizures, and loss of movements that led to be admitted to the Intensive Care Unit. After the diagnosis of porphyria was made, the
patient remained with pain in the lower limbs, being referred to the Pain Department of Santa Casa de Misericórdia de São Paulo. Treatment with
amitriptyline, gabapentin, opioid, and simple analgesics was instituted; however, the patient continued to present recurring episodes of porphyria
and, feeling insecure with the conduction of the case, she stopped the treatment.
Conclusions: Porphyria is one of the rare groups of enzymatic disorders that remain unknown by the great majority of health professionals.
Upon recognizing this lack of knowledge about the disease, the level of stress and insecurity of the patient increases hindering adhesion to and
continuity of the treatment.
Keywords: DISEASES, Hematologic: porphyria; PAIN: neuropathic.
[Rev Bras Anestesiol 2010;60(6): 634-638] ©Elsevier Editora Ltda.
INTRODUCTION
Porphyrias are a group of inherited or acquired disorders involving heme synthesis. The term porphyria derives from the
Greek, meaning purple. This name is attributed to a German
medical student, Schultz, in 1874, referring to the purplish
discoloration of bodily fluids of patients during the episodes.
It has an incidence of 5/100,000 people in the general population while in the psychiatric population the incidence of
acute intermittent porphyria is up to 1/500 patients, and untreated porphyria can be an important cause of psychiatric
Received from the Department of Pain and Palliative Care of Santa Casa de Misericórdia de
São Paulo (SCSP), SP, Brazil.
1. Anestheiologist in Pain Treatment Post-Graduation at CET/SBA of SCSP
2. PhD in Medicine from UNIFESP, Coresponsible for the CET/SBA of SCSP; Coordinator of
the Pain Department of SCSP
3. Assisting Physician of the Anesthesiology and Pain Department of SCSP
Submitted on May 4, 2010.
Approved on June 28, 2010.
Correspondence to:
Dr. Alysson B O Santos
Av Chibarás, 44, AP 1301
Planalto Paulista
04076-000 – São Paulo, SP
E-mail: alyssonbruno@hotmail.com
634
disorders 1. Porphyria has two types of presentation, acute
and cutaneous. Acute manifestations affect especially the
central nervous system, resulting in abdominal pain, vomiting,
acute neuropathy, seizures, and mental alterations including
hallucinations, depression, paranoia, and anxiety. In case of
involvement of the autonomous nervous system, patients can
develop constipation, increase or decrease in blood pressure, tachycardia, and other cardiac arrhythmias. In severe
cases, electrolyte imbalances with hyponatremia, paralysis
of the medulla with respiratory arrest, and psychiatric disorders resulting in suicide, may develop. Its physiopathogeny
is probably linked to the toxic effects of porphyrin precursors,
δ-aminolevulinic acid (ALA) and porphobilinogen (PBG), and
it can be triggered by drugs (such as barbiturates, alcohol,
carbamazepine, carisoprodol, clonazepam, diclofenac, metoclopramide, phenytoin and valproic acid, sulfa drugs, oral contraceptives, sedatives, and antibiotics), severe carbohydrate
restriction, or metabolic stress induced by infections or surgical interventions. Cutaneous porphyrias affect primarily the
skin leading to photosensitivity, bullae, necrosis of the skin
and gingiva, pruritus, edema, and an increase of hairs in areas such as the forehead. The present report describes the
case of a patient with neuropathic pain secondary to porphyria
and the difficulties of the diagnosis and management of the
patient with this painful presentation are discussed.
Revista Brasileira de Anestesiologia
Vol. 60, No 6, November-December, 2010
NEUROPATHIC PAIN IN A PATIENT WITH PORPHYRIA. CASE REPORT
CASE REPORT
DISCUSSION
This is a 27 years old female who was referred to the pain
outpatient clinic of Santa Casa de Misericórdia de São Paulo
by her endocrinologist with complaints of leg pain. The patient reported pain in the lower limbs for approximately 12
years, but after her hospitalization 5 months ago the pain
worsened. Initially, it was believed that obesity was responsible for her pain. The patient was treated with sibutramine
for 20 days and diet with restriction of carbohydrates, and
she developed severe abdominal pain which led to an urgent laparotomy, which did not show any changes. In the
second postoperative day, the patient developed seizures.
She was transferred to the intensive care unit (ICU) where
the presence of elevated liver enzymes and persistent hyponatremia was observed (115 mEq.L-1) even after sodium
replacement. Upon discharge from the ICU, the patient did
not show movements of the upper and lower limbs and she
had severe pain throughout her body that did not respond
to morphine. In the regular ward, she maintained the electrolyte imbalance and loss of movements, and nutritional and
psychiatric follow-up was instituted. Movement of her limbs
returned after resolution of the electrolyte imbalance. Two
urinary analyses were undertaken upon admission to the
hospital; both were negative for porphyria. One day before
being discharged from the hospital, a new urinalysis gave
a positive result. After being discharged from the hospital,
motor disturbances had disappeared, but she remained with
paresthesia and reduction of the sensitivity in the abdominal region until the knees bilaterally. At the moment of the
consultation, the patient complained of pain in the lower limbs, as well as feeling tired and a feeling of increased weight
in her legs, which worsened with a reduction in temperature, without relationship with movements, and with bouts of
worsening of pain in large joints characterized as increased
weight (VAS: 7). She was being treated with tramadol 100
mg every 12 hours as needed. The patient reported that her
father had the same symptoms, but the diagnosis of porphyria was never made and he died due to pneumonia. The
physical exam of the patient failed to show sensorial or motor changes. Electroneuromyography of the lower limbs was
requested, and tramadol 200 mg.day-1, paracetamol, and
amitriptyline 12.5 mg at bed time were prescribed. One month later, the patient returned to the clinic referring partial pain
control (VAS: 6) when gabapentin 300 mg at bedtime was
added to the treatment schedule. However, the patient still
had not had the electroneuromyography. In the following appointment, the patient seemed very mistrustful and she did
not have confidence in the medical care, since she believed
no one really knew how to treat porphyria. She reported another episode in the period between appointments and she
discontinued her medications. Tramadol and simple analgesic were prescribed once more and the patient was oriented
on how to take them. However, the patient did not attend the
follow-up appointment.
This patient had a typical history of acute porphyria. After a period of carbohydrate restriction in her diet, she developed an
acute episode triggered by hypoglycemia that was wrongfully
mistaken as acute abdomen and she underwent a laparotomy.
The surgical stress and drugs contraindicated for those patients
(metoclopramide, ketoprophen, and antibiotics) were used leading to worsening of her symptoms, causing electrolyte imbalances and seizures. Besides neuropathic visceral pain the
patient also developed tetraplegia, and the differential diagnosis with systemic lupus erythematosus and Guillain-Barré syndrome is usually necessary 2-4. Porphyria-induced peripheral
neuropathy is fundamentally motor. Asymmetric paresis, which starts in the proximal upper limbs but that can be focal and
may involve cranial nerves can be seen. Muscle weakness may
progress to respiratory and medullar paralysis and death, especially if the diagnosis is delayed. Even advanced paralysis
is reversible with adequate treatment, but it requires several
months of rehabilitation. Pain can be severe and almost always
requires the use of opioids. Patients who experience frequent
episodes may develop chronic neuropathic pain in the extremities, as well as chronic pain the digestive tract. In those cases,
treatment with long-acting opioids can be indicated. Long-term
complications include hypertension, renal dysfunction, chronic
liver damage, and hepatocellular carcinoma 5,6. Some patients
develop chronic neuropathic pain, which increases the risk of
depression and suicide 7.
Resting the diagnosis on the urine levels of porphobilinogen
(PBG) may be misleading, especially if the urine is collected
between episodes, making it difficult the correct diagnosis and
treatment of this disorder 8. Treatment is based on a carbohydrate-rich diet. In the United States and Great Britain, hematin and
heme arginate are the drugs of choice to treat acute porphyria,
respectively. This disease is usually accompanied by depression
and seizures. Most drugs used to treat seizures potentiate the
condition, making its treatment a problem. Some benzodiazepines are safe and, when used along with anticonvulsants such as
gabapentin offer the possibility of seizure control. Blood transfusion is occasionally used to suppress the production of heme by
the individual. Since involvement of the nervous system caused
by porphyria is due to basically the neurotoxic effects of porphyrin
precursors, amitriptyline associated with gabapentin, opioid, and
simple analgesics was prescribed and an electroneuromyography was requested to confirm the neuronal lesion 9. The lack of
confidence of the patient with received successive treatments,
the lack of knowledge of professionals about its pathology, and
the absence of guidance to the patient about factors that can
trigger an episode led to the difficulty of her acceptance for the
treatment proposed.
The diagnosis of porphyria described in the XIX Century
continues to be delayed, which exposes patients to inadequate treatments, worsening even more their situation. This reality
will last as long as physicians do not have the differential diagnosis of porphyria in mind when facing young patients with
severe abdominal pain associated with neuropathies and/or
electrolyte imbalances.
Revista Brasileira de Anestesiologia
Vol. 60, No 6, November-December, 2010
635
SANTOS, GOZZANI, GROKE
REFERÊNCIAS / REFERENCES
01. Tishler PV, Woodward B, O’ Connor J et al. – High prevalence of
intermittent acute porphyria in a psychiatric patient population. Am J
Psychiatry, 1985;142:1430-1436.
02. Wikberg A, Andersson C, Lithner F – Signs of neuropathy in the lower
legs and feet of patients with acute intermittent porphyria. J Intern
Med, 2000;248:27-32.
03. Albers JW, Fink JK – Porphyric neuropathy. Muscle Nerve, 2004;
30:410-422.
04. Roelandts R – The diagnosis of photosensitivity. Arch Dermatol,
2000;136:1152-1157.
05. Ostrowski J, Kostrzewska E, Michalak T et al. – Abnormalities in liver
function and morphology and impaired aminopyrine metabolism in hereditary hepatic porphyrias. Gastroenterology, 1983;85:1131-1137.
06. Linet MS, Gridley G, Nyre’n O et al. – Primary liver cancer, other malignancies, and mortality risks following porphyria: a cohort study in
Denmark and Sweden. Am J Epidemiol, 1999;149:1010-1015.
07. Jeans JB, Savik K, Gross CR et al. – Mortality in patients with acute
intermittent porphyria requiring hospitalization: a United States case
series. Am J Med Genet, 1996;65:269-273.
08. Anderson KE, Bloomer JR, Bonkovsky HL et al. – Recommendations
for the diagnosis and treatment of the acute porphyrias. Ann Intern
Med, 2005;142:439-450.
09. Lin CSY, Krishnan AV, Lee MJ et al. – Nerve function and dysfunction
in acute intermittent porphyria. Brain, 2008;131:2510-2519.
Resumen: Santos ABO, Gozzani JL, Groke DF – Dolor Neuropático
en Paciente con Porfiria: Relato de Caso.
638
Justificativa y objetivos: Las porfirias son un grupo de disturbios heredados o adquiridos que involucran las enzimas participantes en el
proceso de síntesis del grupo hemo. Las manifestaciones agudas
afectan el sistema nervioso, trayendo como resultando el dolor abdominal, vómitos, neuropatía aguda, convulsiones y disturbios mentales. La fisiopatogenia es el resultado del efecto tóxico de los precursores de la porfirina, pudiendo ser desencadenada por fármacos
usados como rutina en la práctica médica, la restricción intensa de
carbohidratos y por el estrés metabólico. El objetivo de este trabajo
fue presentar un caso de porfiria de diagnóstico tardío, que evolucionó para dolor crónico.
Relato del caso: Paciente del sexo femenino, 27 años, ingresada
hace 5 meses, con dolor abdominal intenso sin diagnóstico clínico.
Fue indicada la laparotomía exploradora, que no mostró la causa
para el cuadro. La paciente, expuesta al trauma quirúrgico y a los
medicamentos que desencadenan crisis de porfiria, como el ceprofeno, la metoclopramina y los antibióticos, evolucionó con importante
hiponatremia, elevación de enzimas hepáticas, convulsión y pérdida
de los movimientos, y tuvo que ser ingresada en una Unidad de Cuidados Intensivos. Después del diagnóstico de porfiria, continuó con
el dolor en los miembros inferiores y tuvo que ser derivada al Servicio
de Dolor de la Santa Casa de Misericordia de São Paulo para tratamiento. Empezó el tratamiento con amitriptilina, gabapentina, opioide
y analgésicos sencillos, pero continuó presentando crisis recurrentes
de porfiria y como estaba insegura en cuanto a la conducción del
caso, abandonó el acompañamiento.
Conclusiones: La porfiria es uno de los raros grupos de disturbios
enzimáticos que permanecen sin conocerse por una gran parte de los
profesionales de la salud. El paciente, al darse cuenta que no conoce
la enfermedad, se estresa mucho más y se siente muy inseguro con
respecto al tratamiento, dificultando su aplicación y continuidad.
Revista Brasileira de Anestesiologia
Vol. 60, No 6, Novembro-Dezembro, 2010