Porphyria cutanea tarda

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Porphyria cutanea tarda is the commonest porphyria and is a hepatic, predominantly acquired disorder rather than an acute neurovisceral porphyria. Uroporphyrins build up in liver, circulate and deposit around superficial dermal vessels. Light in the near-ultraviolet and visible violet range activates them, producing oxidative vessel and junctional injury. The result is painless fragility, vesicles and bullae on dorsal hands, fingers and forearms, often after trivial trauma. Healing leaves milia, scars and mottled hypo- or hyperpigmentation.

The enzyme inhibition usually requires a combination of hepatic oxidative stress and iron. Alcohol, hepatitis C, HIV, oestrogen, smoking, iron overload and haemochromatosis variants are important associations. A minority has inherited partial enzyme deficiency, but penetrance still depends on acquired factors. Because PCT can reveal chronic viral hepatitis, fibrosis or iron-loading disease, dermatological confirmation opens a liver-health pathway rather than ending at blister treatment.

Treatment lowers hepatic iron or mobilises excess porphyrin slowly. Serial venesection is usually preferred when feasible. Very low-dose hydroxychloroquine is an alternative, not the standard daily anti-inflammatory dose. Skin can remain fragile for months while biochemical remission develops, and relapse follows return of an untreated driver. Liver-fibrosis assessment and appropriate hepatocellular-carcinoma surveillance are based on underlying liver disease, not on hand blisters alone.

Key points

Porphyria cutanea tarda causes painless skin fragility, vesicles and tense bullae on sun-exposed backs of hands and forearms, followed by crust, milia, scarring and pigment change.
Facial hypertrichosis and hyperpigmentation can accompany the hand disease; erythema may be minimal and ordinary window glass does not block all porphyrin-activating visible light.
Reduced hepatic uroporphyrinogen decarboxylase activity permits oxidised porphyrins to accumulate, circulate and absorb light energy in superficial skin vessels.
Confirm excess and pattern with protected urine and plasma porphyrins, adding faecal fractionation through a specialist laboratory; urine porphobilinogen is not the diagnostic test for PCT.
Investigate iron status, liver tests and fibrosis, hepatitis C, HIV, alcohol, smoking, oestrogen exposure and HFE variants because treatment of acquired drivers prevents relapse.
Preferred disease-directed therapy is specialist venesection, commonly about 450 mL every one to two weeks while haemoglobin and ferritin are monitored to a low-normal target without causing anaemia.
Low-dose hydroxychloroquine 100 mg twice weekly is an alternative when venesection is unsuitable; ordinary daily rheumatology dosing can mobilise porphyrin too rapidly and injure the liver.
Stop alcohol and unnecessary iron, review oestrogen and treat hepatitis C or HIV with the relevant specialist; do not stop necessary therapy without an agreed substitute.
Use gloves, sleeves, shade and opaque physical barriers against visible violet light while porphyrins fall; ordinary UV sunscreen alone may not prevent blistering.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Acquired hepatic enzyme inhibition

Most disease arises when hepatic oxidative stress inhibits uroporphyrinogen decarboxylase despite no inherited enzyme deficit in other tissues.

Iron and alcohol exposure

Hepatic iron loading and sustained alcohol exposure promote oxidative conditions that reduce enzyme activity and amplify porphyrin accumulation within the liver.

Viral and hormonal drivers

Hepatitis C, HIV and oestrogen exposure increase susceptibility and should be sought because each has a distinct modifiable pathway.

Familial partial deficiency

A minority inherits reduced enzyme activity in all tissues, but clinical PCT still usually requires iron or another acquired hepatic factor.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Porphyrin synthesis stalls
Reduced uroporphyrinogen decarboxylase activity prevents orderly haem synthesis and permits highly carboxylated porphyrins to accumulate in liver and plasma.
2
Light activates stored porphyrin
Near-ultraviolet and visible violet energy excites porphyrins in superficial skin, generating reactive oxygen species around dermal vessels.
3
The junction becomes fragile
Repeated photo-oxidative damage weakens structural proteins at the dermal–epidermal interface, so relatively minor hand trauma forms cell-poor subepidermal blisters.
4
Iron sustains the block
Iron-driven oxidation maintains inhibitory metabolites inside hepatocytes, explaining why controlled depletion restores enzyme function and reduces porphyrins.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Dorsal-hand fragility

Minor knocks produce erosions, crust or peeling over backs of hands and fingers, often before the patient notices intact bullae.

Painless exposed-site bullae

Clear tense vesicles and blisters form on sun-exposed hands or forearms without the intense itch of autoimmune pemphigoid.

Milia and scarring

Small white keratin cysts, mottled pigment and thin scars remain after repeated blisters and provide evidence of chronic recurrence.

Facial hypertrichosis

New coarse temple, cheek or forehead hair with facial pigmentation can accompany PCT and should be distinguished from androgen-pattern hirsutism.

Dark urine

Porphyrin-rich urine may appear red-brown or darken on standing, but urine colour is neither required nor sufficiently specific for diagnosis.

Liver-disease warningRed flag

Jaundice, ascites, hepatomegaly, splenomegaly, weight loss, bleeding or encephalopathy demands expedited liver assessment beyond routine PCT care.

Red flags requiring action

Painful inflamed blisters, extensive mucosal disease, neuropathy or abdominal crisis symptoms are atypical for porphyria cutanea tarda, while jaundice, weight loss, hepatomegaly, ascites or cognitive change requires expedited hepatic assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Urine and plasma total porphyrinsFirst step
Why
Demonstrate substantial porphyrin excess using specimens protected from light.
Interpretation and limitations
Marked uroporphyrin-predominant elevation supports PCT, but total concentration alone does not identify every porphyria and should enter specialist fractionation.
02
Urine, plasma and faecal porphyrin fractionation
Why
Confirm the PCT biochemical pattern and distinguish variegate or hereditary coproporphyria.
Interpretation and limitations
Specialist laboratories interpret uroporphyrin, heptacarboxyl and isocoproporphyrin patterns; light exposure, collection and renal function can alter results.
03
Urine porphobilinogen when acute symptoms exist
Why
Assess a separate acute hepatic porphyria when neurovisceral attacks enter the differential.
Interpretation and limitations
Porphobilinogen is usually not elevated in isolated PCT, so a normal result neither proves nor excludes the cutaneous porphyrin pattern.
04
FBC, ferritin and transferrin saturation
Why
Assess iron burden and create a safe venesection baseline.
Interpretation and limitations
Ferritin rises with inflammation and liver injury; interpret saturation and haemoglobin together and test HFE variants when iron phenotype or family history supports it.
05
Liver and viral assessment
Why
Identify hepatitis C, HIV, alcohol-related injury, fibrosis and other treatable hepatic drivers.
Interpretation and limitations
Request liver profile, hepatitis C antibody with confirmatory RNA, HIV testing with consent and non-invasive fibrosis assessment; image or refer from liver risk rather than skin extent.
06
Skin biopsy
Why
Resolve an atypical mechanobullous eruption when biochemical testing and morphology do not align.
Interpretation and limitations
Histology can show a cell-poor subepidermal blister and vessel-wall material but is not specific; porphyrin biochemistry confirms the metabolic diagnosis.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Epidermolysis bullosa acquisita

Trauma-site mechanobullous lesions, milia and scar overlap, but type VII collagen immunopathology and absent porphyrin excess distinguish acquired epidermolysis.

Bullous pemphigoid

Intense itch, urticarial inflammation and generalised flexural bullae with linear IgG or C3 differ from painless light-exposed fragility.

Pseudoporphyria

A similar hand eruption associated with medicines or renal failure has normal porphyrin studies and therefore requires exposure or dialysis assessment.

Phototoxic drug reaction

Acute erythema and burning in a medication-shaped light distribution usually lacks the chronic milia, fragility and biochemical porphyrin pattern.

Other cutaneous porphyria

Variegate or hereditary coproporphyria can blister and also cause acute neurovisceral attacks, requiring full fractionation rather than morphology alone.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First diagnostic sequenceConfirm porphyrins and map hepatic driversFirst stepPainless sun-exposed hand fragility, bullae, milia or facial hypertrichosis suggests PCT.

1Document exposure distribution, trauma, urine colour, alcohol, smoking, oestrogen, iron, medicines and liver or neurovisceral symptoms and photograph representative lesions with consent.
2Send light-protected urine and plasma for porphyrin quantification and specialist fractionation, adding faecal analysis and acute porphobilinogen only when the laboratory or phenotype indicates.
3Assess FBC, iron indices, liver function and fibrosis, hepatitis C, HIV and HFE context and refer jointly to dermatology and a porphyria or liver service.

02Preferred iron reductionUse serial venesection to biochemical remissionPreferredPCT is confirmed and venesection is feasible without limiting anaemia or vascular-access problems.

1Agree a specialist schedule, commonly removing about 450 mL every one to two weeks, with haemoglobin and ferritin checked often enough to prevent excessive depletion.
2Continue until the service's low-normal ferritin target and falling porphyrins indicate iron reduction, then stop rather than producing symptomatic deficiency.
3Follow skin fragility, porphyrins, ferritin and the treated hepatic driver over months, using maintenance venesection only for documented biochemical relapse or recurrent iron loading.

03Alternative porphyrin clearanceUse genuinely low-dose hydroxychloroquineAlternativeVenesection is unsuitable, inaccessible or declined and liver assessment permits an antimalarial strategy.

1Check liver, renal, eye, cardiac, interaction and reproductive context and confirm that the prescribed dose is 100 mg twice weekly rather than a routine daily rheumatology dose.
2Monitor liver tests and porphyrins during early mobilisation and stop or reassess for substantial biochemical worsening or systemic symptoms.
3Continue until biochemical remission under specialist care, then stop and follow for relapse instead of leaving indefinite unreviewed treatment.

04Remove and treat driversMake remission durableAlcohol, viral hepatitis, oestrogen, smoking, iron or another hepatic factor is identified.

1Offer supported alcohol and smoking change and stop unnecessary iron while avoiding blame and assessing withdrawal risk or nutritional need.
2AlternativeCoordinate hepatitis C cure, HIV treatment, haemochromatosis care and an alternative to oestrogen with the relevant specialist rather than changing essential medicines in isolation.
3Use liver-stage appropriate surveillance and repeat porphyrins when skin recurs, because persistent scars alone do not prove biochemical relapse.

Key medicines and prescribing safety1 treatment · regimens, roles and cautions

Mobilises stored hepatic porphyrins when venesection is unsuitable or declined.

Low-dose hydroxychloroquine for PCT

Take 100 mg by mouth twice weekly under a specialist porphyria regimen until biochemical remission, then stop according to porphyrin and liver response.

This dose is deliberately far below ordinary daily inflammatory-disease dosing; excessive dosing can cause abrupt porphyrin release and hepatotoxicity. Check liver, kidney, eye, QT and interaction risks and avoid unsupervised use in pregnancy.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Scarring and secondary infection

Repeated trauma and blistering leave milia, dyspigmentation and scars, while open hands can develop painful bacterial infection.

Chronic liver fibrosis

Alcohol, viral hepatitis and iron overload can independently and jointly progress to advanced fibrosis or cirrhosis.

Hepatocellular carcinoma

Cancer risk reflects chronic hepatic injury and fibrosis, requiring surveillance according to liver stage rather than cutaneous activity alone.

Treatment-induced anaemia or hepatitis

Excessive venesection depletes iron and haemoglobin, while overly rapid antimalarial porphyrin mobilisation can acutely injure liver.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

During venesection track haemoglobin and ferritin at the specialist interval, delaying treatment before symptomatic anaemia or excessive iron depletion develops.
During low-dose hydroxychloroquine monitor liver tests and plasma or urine porphyrin decline and review nausea, rash, visual, cardiac or hypoglycaemic symptoms.
Record new blisters and fragility separately from milia, scars and pigment that can persist after biochemical control.
Confirm completion and response of hepatitis C, HIV, alcohol, oestrogen or haemochromatosis treatment and reassess relapse risk if exposure changes.
Follow fibrosis and hepatocellular-carcinoma surveillance through hepatology when the underlying liver stage requires it.
Repeat fractionated porphyrins for recurrent active lesions rather than restarting venesection from appearance alone.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

This porphyria is not an attack

PCT primarily affects skin and liver; acute abdominal pain, neuropathy and psychiatric attacks suggest a different hepatic porphyria and need porphobilinogen testing.

Window light can remain active

Porphyrins absorb visible violet wavelengths that pass through ordinary glass, explaining hand disease in drivers and incomplete protection from standard UV filters.

Iron acts inside the liver

Even modest iron excess can support oxidative enzyme inhibition, so venesection works through hepatic biochemistry rather than by treating blood viscosity.

Low dose is a safety mechanism

Hydroxychloroquine slowly releases porphyrin for excretion; normal daily dosing can mobilise too much and acutely worsen liver injury.

Skin lags laboratory

Fragility improves after porphyrins fall, while scars and milia persist, so residual marks do not justify continuing iron removal beyond the target.

11Common pitfallsFrequent interpretation and management errors.

01
Ordering urine porphobilinogen alone and declaring a normal result excludes PCT.
02
Diagnosing autoimmune pemphigoid from tense blisters without recognising exposed-hand fragility and milia.
03
Starting venesection without haemoglobin, iron and liver assessment or continuing into symptomatic deficiency.
04
Prescribing hydroxychloroquine at an ordinary daily lupus dose for PCT.
05
Treating hand lesions while failing to test hepatitis C, HIV, iron overload and liver fibrosis.
06
Relying on ordinary ultraviolet sunscreen without physical protection from visible violet light.