Symptoms: Does your patient have a porphyria?

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Symptoms: Does your patient have a porphyria?

According to Anderson et al (Annals of Internal Medicine, 2005, 142(6): 441), approximately 80% of individuals who carry a gene mutation for acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria remain asymptomatic, and others may have only one or a few acute attacks throughout life. In most of these cases the levels of ALA, porphobilinogen, and porphyrins in urine, serum, and feces are normal. Additionally, most patients with ALA-dehydratase deficiency porphyria, who may have less than 5% of normal ALA dehydratase activity, also remain asymptomatic for most of their lives. Severe neuropathic abdominal pain, the most frequent symptom, is diffuse rather than localized and is often accompanied by nausea, vomiting, distention, constipation, and sometimes diarrhea. Other symptoms include insomnia (often an early symptom), heart palpitations, seizures (sometimes due to hyponatremia), restlessness, hallucinations, and other acute psychiatric symptoms.

Table 1. Common Presenting Symptoms and Signs of Acute Porphyria*

Signs and Symptoms	Estimated Incidence (%)	Comment
Gastrointestinal
Abdominal pain	85-95	Usually unremitting (for hours or longer) and poorly localized but can be cramping. Neurologic in origin and rarely accompanied by peritoneal signs, fever, or leukocytosis.
Vomiting	43–88	Nausea and vomiting often accompany abdominal pain.
Constipation	48–84	May be accompanied by bladder paresis.
Diarrhea	5–12
Neurologic
Pain in extremities, back, chest, neck, or head	50–70	Pain may begin in the chest or back and move to the abdomen. Extremity pain indicates involvement of sensory nerves, with objective sensory loss reported in 10%–40% of cases.
Paresis	42–68	May occur early or late during a severe attack. Muscle weakness usually begins proximally rather than distally and more often in the upper than lower extremities.
Respiratory paralysis	9–20	Preceded by progressive peripheral motor neuropathy and paresis.
Mental symptoms	40–58	May range from minor behavioral changes to agitation, confusion, hallucinations, and depression.
Convulsions	10–20	A central neurologic manifestation of porphyria or due to hyponatremia, which often results from syndrome of inappropriate antidiuretic hormone secretion or sodium depletion.
Cardiovascular
Tachycardia	28, 64–85	May warrant treatment to control rate, if symptomatic.
Systemic arterial hypertension	36–55	May require treatment during acute attacks, and sometimes becomes chronic.

* Based on several series of patients with symptomatic acute intermittent porphyria.

K. E. Anderson, J. R. Bloomer, H. L. Bonkovsky, J. P. Kushner, C. A. Pierach, N. R. Pimstone, R. J. Desnick. Recommendations for the Diagnosis and Treatment of the Acute Porphyrias. Annals of Internal Medicine, 2005, 142(6): 441.

The Cutaneous Porphyrias

The most common presenting symptoms among individuals with one of the cutaneous porphyrias are photosensitivity and/or skin fragility. Photosensitivity presents within minutes of exposure to sun and some types of artificial light with severe burning pain especially on the back of the hands, the face, and the top of the feet. Attacks may last for 2–3 days, and are usually unresponsive to any analgesia except cold air and cold water. Except in EPP, this is often accompanied by painful blisters which can take weeks to heal, may become hemorrhagic, and result in scarring and hyper- and hypopigmentation at the sites of the blisters. In CEP, this photosensitivity may lead to mutilation and loss of facial features and fingers. Patients with PCT, HEP, and CEP may also present with hypertrichosis, typically on the temples, usually subtle, but sometimes mimicking hirsutism. Additionally in CEP, erythrodontia with brownish-colored teeth which fluoresce under ultraviolet light and mild or severe hemolytic anemia are common.

Table 2. Common Presenting Signs and Symptoms of Cutaneous Porphyria

Signs and Symptoms	CEP	PCT and HEP	EPP	HCP	VP
Photosensitivity	X	X	X	X	X
Skin fragility	X	X	X	X	X
Blistering	X	X		X	X
Scarring	X	X		X	X
Hyper- and hypopigmentation	X	X
Hypertrichosis	X	X
Anemia	X
Erythrodontia	X
Bone fragility (due to Vitamin D deficiency)	X	X	X	X	X