porphyria cutanea tarda ( pct ) is the most common type of porphyria worldwide , affecting sun - exposed areas of the skin , manifested by cutaneous fragility , vesicobullae , atrophic scarring and formation of milia .
this condition is a disorder of heme biosynthesis caused by a catalytic deficiency in uroporphyrinogen decarboxylase .
there are inherited , acquired and toxic forms of the condition and diagnosis is confirmed based on skin symptoms and porphyrin analysis of urine , blood and stool . without clinical suspicion for this important diagnosis the necessary investigations may not be performed , resulting in a delay of diagnosis and treatment .
we present the cases of two patients who were initially misdiagnosed with epidermolysis bullosa acquisita ( eba ) predominantly based on histopathology but were subsequently diagnosed with pct on porphyrin studies due to clinical suspicion .
a 36-year - old female presented with a 6-month history of blisters on the dorsal aspects of her hands bilaterally with associated fragility and photosensitivity .
this was also associated with a 2-year history of increased hair growth on her cheeks .
she had been previously treated with oral antibiotics and topical steroid with no obvious improvement .
the patient had a medical background of asthma for which she was using twice daily fluticasone / salmeterol inhalations and salbutamol inhalations as required .
her only other medication was the oral contraceptive pill , which she had been taking long - term .
the patient had multiple blisters and erosions distributed over the dorsa of her hands with a number of milia ( fig .
1 ) . a punch biopsy of the right hand index finger and a perilesional biopsy of the left hand were performed .
histopathology showed a partly regenerated subepidermal blister with a heavy inflammatory cell infiltrate between the old roof and the regenerating base ( fig .
the pattern was recognized as the  u - serrated pattern , typical of antibodies to type vii collagen .
based on these findings , eba was diagnosed and salt split skin preparation was not performed .
although the initial attending doctor was dissuaded from a diagnosis of pct on the basis of histology findings , subsequent review favoured pct clinically and porphyrin studies later confirmed this ( table 1 ) .
the patient had deranged liver function tests , but her liver screen did not demonstrate any abnormalities , including negative hepatitis b / c and hiv serologies and normal iron studies and alpha fetoprotein levels .
desmoglein 1 and 3 reactivity and subsequent collagen vii reactivity testing were all negative , excluding a concomitant diagnosis of pemphigus or eba .
the patient was commenced on hydroxychloroquine 200 mg twice weekly and was given advice on mechanical and photoprotection .
she was also commenced on regular venesections , aiming for a ferritin level of 50 g / l to improve pct symptoms .
a 50-year - old female presented for a second opinion after a 3-year history of spontaneous blistering affecting the extensor surfaces of her hands and forearms with associated scarring .
she had been diagnosed with eba by a previous clinician based on biopsy histopathology findings 3 months earlier .
there was a cell - poor subepidermal vesicle containing only a few lymphocytes and with festooning of the dermal papillae and very little dermal inflammatory infiltrate seen ( fig .
direct immunofluorescence studies revealed positive staining for igg in a linear pattern along the dermoepidermal junction .
all other markers were negative and salt split skin studies could not be performed due to technical difficulties .
the patient was initially treated with potent topical corticosteroids as well as low - dose oral corticosteroids and was still experiencing flares .
she was then tried on 100 mg of oral doxycycline , which resulted in some improvement .
she also reported a positive family history for blistering of the hands affecting her maternal grandmother but no known family history of liver disease .
she had been taking the oral contraceptive pill for many years but had recently ceased taking this . on examination ,
the dorsal aspects of both hands were erythematous , with evidence of milia and post - inflammatory hyperpigmentation ( fig .
based on this clinical appearance , further testing was performed , including full blood count , renal function , electrolytes and liver function , which were all normal .
in addition no hfe mutations were detected and hepatitis b / c and hiv serologies were negative .
further urine and stool porphyrin studies showed elevated urine porphyrin , faecal porphyrin and porphyria / creatinine ratio , which confirmed the diagnosis of pct ( table 1 ) .
desmoglein 1 and 3 reactivity and collagen vii reactivity testing were negative , excluding a concomitant diagnosis of pemphigus or eba .
she was also advised to use gloves and zinc oxide sunscreen to provide physical protection .
a 36-year - old female presented with a 6-month history of blisters on the dorsal aspects of her hands bilaterally with associated fragility and photosensitivity .
this was also associated with a 2-year history of increased hair growth on her cheeks .
she had been previously treated with oral antibiotics and topical steroid with no obvious improvement .
the patient had a medical background of asthma for which she was using twice daily fluticasone / salmeterol inhalations and salbutamol inhalations as required .
her only other medication was the oral contraceptive pill , which she had been taking long - term .
the patient had multiple blisters and erosions distributed over the dorsa of her hands with a number of milia ( fig .
1 ) . a punch biopsy of the right hand index finger and a perilesional biopsy of the left hand were performed .
histopathology showed a partly regenerated subepidermal blister with a heavy inflammatory cell infiltrate between the old roof and the regenerating base ( fig .
the pattern was recognized as the  u - serrated pattern , typical of antibodies to type vii collagen .
based on these findings , eba was diagnosed and salt split skin preparation was not performed .
although the initial attending doctor was dissuaded from a diagnosis of pct on the basis of histology findings , subsequent review favoured pct clinically and porphyrin studies later confirmed this ( table 1 ) .
the patient had deranged liver function tests , but her liver screen did not demonstrate any abnormalities , including negative hepatitis b / c and hiv serologies and normal iron studies and alpha fetoprotein levels .
desmoglein 1 and 3 reactivity and subsequent collagen vii reactivity testing were all negative , excluding a concomitant diagnosis of pemphigus or eba .
the patient was commenced on hydroxychloroquine 200 mg twice weekly and was given advice on mechanical and photoprotection .
she was also commenced on regular venesections , aiming for a ferritin level of 50 g / l to improve pct symptoms .
a 50-year - old female presented for a second opinion after a 3-year history of spontaneous blistering affecting the extensor surfaces of her hands and forearms with associated scarring .
she had been diagnosed with eba by a previous clinician based on biopsy histopathology findings 3 months earlier .
there was a cell - poor subepidermal vesicle containing only a few lymphocytes and with festooning of the dermal papillae and very little dermal inflammatory infiltrate seen ( fig .
direct immunofluorescence studies revealed positive staining for igg in a linear pattern along the dermoepidermal junction .
all other markers were negative and salt split skin studies could not be performed due to technical difficulties .
the patient was initially treated with potent topical corticosteroids as well as low - dose oral corticosteroids and was still experiencing flares .
she was then tried on 100 mg of oral doxycycline , which resulted in some improvement .
she also reported a positive family history for blistering of the hands affecting her maternal grandmother but no known family history of liver disease .
she had been taking the oral contraceptive pill for many years but had recently ceased taking this . on examination ,
the dorsal aspects of both hands were erythematous , with evidence of milia and post - inflammatory hyperpigmentation ( fig .
based on this clinical appearance , further testing was performed , including full blood count , renal function , electrolytes and liver function , which were all normal .
in addition no hfe mutations were detected and hepatitis b / c and hiv serologies were negative .
further urine and stool porphyrin studies showed elevated urine porphyrin , faecal porphyrin and porphyria / creatinine ratio , which confirmed the diagnosis of pct ( table 1 ) .
desmoglein 1 and 3 reactivity and collagen vii reactivity testing were negative , excluding a concomitant diagnosis of pemphigus or eba .
she was also advised to use gloves and zinc oxide sunscreen to provide physical protection .
pct is a metabolic disorder which can result in the development of hepatocellular carcinoma , advanced liver fibrosis and also liver cirrhosis if cutaneous manifestations are not recognized and properly investigated .
there are multiple genetic and environmental triggers of pct , most commonly including alcohol abuse , oestrogens and liver disease .
other triggering factors include polychlorinated hydrocarbons , iron , viral infections ( such as hepatitis c and hiv ) , dialysis in patients with renal failure and the inheritance of specific mutations in the hfe gene which underlies classic haemochromatosis .
treatment of pct includes withdrawal of precipitating triggers , phlebotomy and oral anti - malarial agents .
the most common symptomatic complaints of patients with pct are due to cutaneous manifestations which can occur after sun exposure or minor trauma .
these include increased photosensitivity and skin fragility with vesicles / bullae and erosions / crusts on sun - exposed sites such as the dorsa of the hands .
crusting of lesions can then take weeks to heal , resulting in atrophic scarring with milia formation .
post - inflammatory hyperpigmentation , scarring alopecia , hypertrichosis and morpheaform / sclerodermoid changes can be also seen .
histological examination of involved skin is not required to confirm the diagnosis of any cutaneous porphyria , rather skin biopsies are obtained to exclude other entities in the differential diagnosis , including eba , drug - induced pseudoporphyria and phototoxic / bullous drug eruptions . as demonstrated by our cases , this can lead to potential misdiagnosis due to histological similarities between the vesiculobullous differentials . in pct ,
characteristic histopathological findings include subepidermal blisters , which lack inflammatory infiltrate , with preservation of dermal papillae in the lesion 's floor (  festooning ) . under direct immunofluorescence microscopy , fibrinogen , complement and immunoglobulins , particularly igg , are often present surrounding blood vessels of the papillary dermis and at the dermal - epidermal junction . as shown in our cases
, these findings can be easily confused with eba in particular , which typically shows similar cell - poor subepidermal blisters and direct immunofluorescence microscopy showing igg deposits at the basement membrane zone , however usually targeting type vii collagen .
thus , whilst histological examination is important in excluding other differential diagnoses , it is important for clinicians to recognize the potential for misdiagnosis of pct as a result of findings on histology . in our cases , both patients had skin biopsies reported as eba , and this could lead to inexperienced clinicians accepting this diagnosis and treating accordingly and inappropriately . whilst case 1 was managed correctly with porphyrin studies performed despite eba histopathological findings , in case 2 the histopathological findings were initially accepted and led to misdiagnosis and delay in appropriate pct treatment .
compounding this diagnostic dilemma is the similar clinical appearances of bullae / milia in both eba and pct , which can falsely reassure the clinician not to perform the necessary porphyrin investigations .
these typically include porphyrin analysis of urine , blood and stool which reveal increased urinary elimination of uroporphyrin , hepta - carboxylated porphyrins and coproporphyrin , and increased faecal excretion of isocoproporphyrin . in summary ,
our cases demonstrate the possible difficulty in differentiating pct from eba and the potentially significant consequences of this misdiagnosis . in patients with undifferentiated bullous / erosive skin conditions occurring in photo - distributed regions ,
pct should be considered in the differential diagnosis irrespective of histopathological findings on biopsies and further investigated appropriately . without a healthy clinical suspicion for pct , which is generally more common than eba
, diagnostic porphyrin screening of urine , blood and stool may not be performed , thus leaving the patient untreated and ultimately at increased risk of developing chronic liver disease and possible hepatocellular carcinoma .
 porphyria cutanea tarda ( pct ) is the most common type of porphyria worldwide and is often initially diagnosed when cutaneous manifestations arise . 
 we present two patients where misdiagnosis of pct occurred due to the condition masquerading as epidermolysis bullosa acquisita histologically . in patients with undifferentiated bullous / erosive skin conditions occurring in photo - distributed regions , 
 pct should be considered in the differential diagnosis irrespective of histopathological findings on biopsies and further investigated and treated appropriately . 