patient’s clinical picture is consistent with PCT: the most common porphyria affecting 5–10 persons per 100 000 people. The cause is inhibition of the fifth enzyme in heme biosynthetic pathway: uroporphyrinogen decarboxylase. PCT is associated with several precipitating factors such as haemochromatosis (53%) and uroporphyrinogen decarboxylase mutations (17%), as well as hepatitis C (69%), alcohol (8%), tobacco (81%), oestrogen (6%), and HIV (15%). Typically, patients are >40 year old and male. The clinical picture is of painless blistering lesions in sun exposed areas, typically the back of the hands. Sun exposed skin can be friable, scarred, or develop hypertrichosis. Remission may occur in the winter months, if sunlight exposure is decreased. Urine is brown–reddish, due to excess uroporphyrin. PCT is usually associated with mild abnormal LFTs. Advanced liver disease is uncommon at initial presentation but may be seen in older patients with recurrent disease. Diagnosis is made with an elevated urine or plasma porphyrin with predominantly uroporphyrin and heptacarboxyporphyrin. Erythrocyte porphyrins are usually normal. A total plasma porphyrin measurement may be most useful for initial screening. A skin biopsy reveals subepidermal bullae. Wood’s lamp examination of the urine shows orange red fluorescence.
First line treatment for PCT involves addressing modifiable risk factors: treating hepatitis C or HIV if present, and restricting alcohol, tobacco, and oestrogen. These factors, in combination with hepatic iron depletion via phlebotomy or iron chelation to a target ferritin at the low end of the normal range, often produces remission. Hydroxychloroquine is an alternative to iron depletion. Once in remission, patients may relapse, especially if they drink >4 standard drinks/ day or continue smoking, so urine or plasma uroporphyrin should be measured annually.
Acute intermittent porphyria is an autosomal dominant partial deficiency of the third enzyme of heme synthesis: porphobilinogen deaminase (or hydroxymehtlbilane synthase). 90% of patients are females, typically presenting aged 18–45 with a prodrome of days of severe fatigue and lack of concentration, then worsening abdominal pain, nausea, vomiting, afebrile tachycardia, and neurological signs including weakness dysthesia, and seizures (20% of patients). Risk factors include cytochrome P450 inducers, oral contraceptive pill, and severely restricted caloric intake. Abdominal exam is often unremarkable and blood tests usually show mild liver derangement and hyponatremia. Diagnosis requires elevated porphobilinogen in urine and plasma, often up to 10–150x normal. Urine colour can be unremarkable, however if exposed to light can turn dark amber when heme precursors form uroporphyrin‐like‐pigments. Treatment is primarily supportive: fluids (preferable 10% dextrose in 0.45% saline), antiemetics, analgesics, and anticonvulsants. Of note, many anticonvulsants are not safe in acute porphyria, including phenytoin, valproic acid, carbamazepine, clonazepam. Intravenous heme is the only specific treatment but is not widely available.
Protoporphyria occurs when there is bone marrow overproduction of protoporphyrin. It is typically diagnosed in early childhood, with toddlers develop pain, stinging, oedema, and itching of sun exposed skin often within 10 minutes of being in the sun but can be longer in adults. Total blood porphyrin over five times the upper limit of normal is diagnostic. Urine colour is normal as protoporphyrin is universally excreted into bile. This leads to complications such as gallstones and cholestasis. Treatment with oral beta‐carotene is most effective, but only works in <1/3 of cases. Activated charcoal, and colestipol are also trialled but often ineffective. Avoidance of sunlight is the main treatment for most patients, is associated with vitamin D deficiency in 50% of patients.
Bullous pemphigoid is a subepidermal blistering disorder that most commonly occurs in older adults. The classic skin lesions are urticarial plaques and tense bullae on the trunk and extremities. Intense pruritus is common, and lesions typically do not scar. Cutaneous lichen planus is most commonly expressed as an eruption of shiny, flat, polygonal, violaceous papules. Dermatitis herpetiformis is an autoimmune blistering disease associated with coeliac disease and characterised by intensely itchy polymorphous vesicular lesions located over the extensor surfaces, back, and scalp.
Bissell D, Anderson K, Bonkovsky H. Porphyria. New England Journal of Medicine. 2017;377(9):862–872.
https://www.nejm.org/doi/full/10.1056/NEJMra1608634
8. Answer: C
Rosacea is an inflammatory facial condition of unknown cause associated with high morbidity due to social avoidance, and mood disorder. Rosacea most commonly manifests in middle age, mostly effects women, and can present with flushing and telangiectasia, inflammatory papules and pustules, or a combination of both. Keratitis is commonly seen in rosacea, but is rarely severe enough to be vision threatening. Long‐term sequelae include phymatous changes, most commonly of the nose.
Despite the unclear pathophysiology, several anti‐inflammatory, and vasoactive medications have been shown to significantly improve symptoms associated with the condition. Topical medications blockading alpha‐receptors significantly reduce vascular symptoms – for example brimonidine and oxymetazoline. For inflammatory symptoms, medications such as metronidazole, ivermectin, azelaic acid have shown significant efficacy. For lesions refractory to topical therapy, combination with low‐dose oral doxycycline or tetracycline is indicated, and for cases refractory to this, low‐dose isotretinoin is effective. For inflamed phymatous changes, anti‐inflammatory treatments can be effective, but for more fibrosed lesions, ablative laser therapies can be effective.
van Zuuren E. Rosacea. New England Journal of Medicine. 2017;377(18):1754–1764.
https://www.nejm.org/doi/full/10.1056/NEJMcp1506630?af=R&rss=currentIssue&page=2&sort=newest
9. Answer: B
In developed countries, scabies epidemics occur primarily in nursing homes, prisons and other long‐term care facilities. Transmission of scabies is predominantly through direct skin‐to‐skin contact. Prevalence rates for scabies are higher in sexually active individuals, immunocompromised, and elderly patients. The S scabiei hominis mite that infects humans is female and is large enough (0.3–0.4 mm long) to be seen with the naked eye. Its life cycle occurs completely on the human, but the mite is able to live on bedding, clothes, or other surfaces at room temperature for 2–3 days, while remaining capable of infestation and burrowing.
Patients usually present with pruritus, erythematous papules, and vesicles in webbed spaces of the fingers, wrist, elbows, and scrotum. Burrows are a pathognomonic sign and represent the intraepidermal tunnel created by the moving female mite.
There are three types of scabies:
1 Classic scabies: Typically, 10–15 mites live on the host. After 4 weeks of primary infection and with subsequent infections, a delayed type IV hypersensitivity reaction to the mites and eggs occurs, which causes the classic skin eruption and its associated intense pruritus.
2 Crusted scabies is a distinctive and highly contagious form of the disease. In this variant, hundreds to millions of mites infest the patient, who is usually immunocompromised, elderly, or physically or mentally disabled and impaired. It can be confused with severe dermatitis or psoriasis because widespread, crusted lesions appear with thick, hyperkeratotic scales over the elbows, knees, palms, and soles. Serum IgE and IgG levels are high in patients with crusted scabies, but the immune reaction is not protective. Crusted scabies carries a higher mortality rate than the classic form of the disease, because of the
