Variegate
Porphyria

Summary

  1. Variegate Porphyria is an acute porphyria known to cause skin blisters and sores, muscle weakness, and neurological changes.

  2. Symptoms usually begin in adulthood.

  3. Most symptoms clear after an attack, and with early treatment symptoms usually won't worsen with time.

Variegate Porphyria (VP) is very similar to Acute Intermittent Porphyria (AIP) but affected individuals also have sun sensitivity and skin blistering. It occurs particularly in people with South African heritage.

VP is inherited from one of the parents and usually first manifests in adulthood. Severe abdominal pain with vomiting and constipation is the main feature but pain, numbness and weakness in the arms and legs can also be present as well as palpitations, confusion, agitation, seizures, hallucinations and insomnia.

Triggers include fasting, low carbohydrate intake, alcohol intake, infections and a whole range of drugs which are listed on porphyria websites and should be avoided. In women episodes may coincide with menstruation.

Management consists of avoiding these triggers and dealing urgently with acute attacks.

In acute attacks intravenous glucose and pain relief with opiates, usually morphine is required. If this does not settle the pain haemarginate infusions can result in rapid improvement and may be required on up to four consecutive days. Access to suitable veins is critical and haemarginate needs to be specially prepared and be given through a central line. 

In acute attacks prompt attendance at a hospital emergency department is critical so treatment can be given promptly to relieve symptoms and prevent deterioration.

 

Management Plans

Because treatment needs to be given promptly and is complex its best to always attend the same emergency department and to have an agreed treatment plan spelling out in some detail what needs to happen. This ideally should include the contact details of a porphyria specialist and be agreed to by the patient, the emergency department staff and the porphyria specialist.

Importantly other cause of abdominal pain including appendicitis, cholecystitis endometriosis and bowel inflammation can still occur and must not be overlooked.

Testing

It’s important to confirm the diagnosis of porphyria and to document this clearly in the patient records and plan.

The best time to prove the diagnosis is during an acute attack when levels of porphyrins are high in plasma, in the urine (mostly coproporphrin III) and in the faeces (mostly protoporphyrin). 

 

Skin Changes

The skin features of PCT, HCP and VP are identical. They are caused by excess porphyrin accumulating in the skin (dermis). These porphyrins react to light (visible violet light), which leads to skin damage. This can result in a number of issues including the skin becoming fragile, with easy tearing from minor trauma. PCT, HCP and VP are known as bullous porphyrias, as they all can lead to skin blistering. Fluid, or blood-filled blisters of varying sizes (usually 0.5-1cm) can be seen in sun-exposed sites, particularly the backs of the hands, and to a lesser extent the face, tops of the feet and scalp. (See Figure 1.) These can be slow to heal, leaving sores and scabs which heal leaving marks and scars. Small (~1mm), firm, white lumps known as milia form as blisters heal. These resolve slowly over months to years. (See Figures 1 & 2.) The blisters can be uncomfortable or sore, especially when they are very tense/distended, or when there are open areas. Affected areas can also be itchy as they heal.

 

Increased pigmentation can sometimes be seen in affected areas, particularly in those with darker skin types. (See Figure 3.) Rarely, other skin problems can occur, including hardening of the skin (sclerodermoid change) usually of the chest, excess hair growth (hirsutism or hypertrichosis) especially on cheeks, or scarring hair loss (usually where there have been blisters) and nail changes (nail lifting - onycholysis). (See Figure 1).

 

Skin changes are less common in VP (two thirds of patients have skin changes), and it may be other symptoms such as abdominal pain which will bring these patients to seek medical attention.

 

Strict sun protection is an important part of keeping the skin in good condition. This should be all year round, not just in summer. Sun protection should include wearing long sleeved clothing of a dense enough fabric that when held up to the light, no light comes through. A broad brimmed hat, sunglasses and closed shoes should be worn whenever outdoors. Sunscreen is important, but not as effective as clothing, as visible light can penetrate most sunscreens and reach the porphyrins in the upper part of the skin. Sunscreen should be high in zinc, and ideally opaque (rather than invisible). A tint can help to make the sunscreen more cosmetically appealing, and block more light from penetrating. Car windows should be tinted to the darkest legal tint. Driving gloves are recommended for long car trips. Also consider gloves for gardening, sport and manual labour, to minimise both light exposure and injuries.

 

Treatment of blisters includes puncturing them with a sterile needle to release the fluid, which will result in improved comfort and more rapid healing. A dressing can be used to protect the affected areas while they heal and help to prevent infection. Regular bland moisturiser or hand cream should be applied. Milia can be extracted by pricking the overlying skin and squeezing it out.

 

 


Fig 1.

A typical blister on back of hand. When these break, they become an erosion. There is an erosion on the left index finger, some old scars (4th finger) and milia at the base of the 4th finger. Note the nails that have lifted up off the nail bed causing a white appearance (onycholysis).

 

 

 

 

 

 

 

Fig 2.

Erosions and milia (see left 2nd finger).

 

 

Figure 3.

Pigmentation, erosions.