Anton Borg

High D-dimer levels at presentation in patients with venous thromboembolism is a marker of adverse clinical outcomes.

Qualitative d‐dimer results, together with clinical probability scores, are well established in the diagnosis of venous thromboembolism (VTE). The predictive value of quantitative d‐dimer levels for various clinical outcomes in VTE patients is not fully understood. d‐dimer levels obtained at presentation were analysed in 699 (360 men; 339 women) VTE patients for survival and occurrence of malignancy. Patients were followed for a median of 23 months. 17·2% patients had a d‐dimer level >8000 ng FEU/mlat presentation, which was associated with decreased overall survival (OS) (P < 0·001) and event‐free survival (EFS) (P < 0·001). 25·4% patients had malignancy and 4% subsequently developed malignancy following VTE. 29·9% of patients with VTE and malignancy had a d‐dimer level >8 mg/l when compared with 13·4% of patients with VTE without malignancy (P < 0·001). 50% of patients who developed subsequent malignancy following VTE had a presentation d‐dimer >8000 ng FEU/mlas compared with 13·3% of patients with VTE with out malignancy (P = 0·009). In conclusion, d‐dimer >8000 ng FEU/ml at presentation in patients with VTE is a marker of poor OS, EFS and underlying malignancy. Consideration of screening for malignancy is recommended in patients with VTE with a presentation d‐dimer >8000 ng FEU/ml and age >60 years.

Flagellate erythema due to bleomycin.

A 48-year-old woman, recently diagnosed with classical Hodgkin lymphoma stage 3B, developed an intensely itchy rash 1 week after her first cycle of doxorubicin, bleomycin, vincristine, dacarbazine (ABVD) chemotherapy. The eruption subsided with a course of prednisolone 40 mg daily for 4 d, but recurred after the third chemotherapy cycle, despite the omission of bleomycin. She was referred to dermatology at this stage. Examination showed an extensive violaceous and erythematous excoriated rash with a striking linear configuration and post-inflammatory hyperpigmentation, typical of flagellate erythema. Clobetasol proprionate cream twice daily was prescribed with good response. After 1 week, the inflammatory lesions had settled, leaving residual hyperpigmentation that was expected to settle with time. There has been no recurrence at 3 months follow-up. Flagellate erythema is a cutaneous side effect of bleomycin or its derivative peplomycin. The term ‘flagellate’ derives from the Latin flagellum, referring to the characteristic whip-like appearance. It is also rarely associated with ingestion of shiitake mushrooms, dermatomyositis and adult-onset Still’s disease. All methods of administration of bleomycin may cause the rash, occurring from 12 h to as long as 6 months after drug administration. The rash usually subsides 3–4 months following discontinuation of the drug. It is unusual that our patient had a relapse after chemotherapy omitting bleomycin, suggesting a possible unusual recall phenomenon, particularly as flagellate erythema has not been described with the other drugs in the ABVD regime. Treatment includes topical or systemic corticosteroids and oral antihistamines. The length of treatment depends on clinical response. The mechanism for the peculiar linear nature of this reaction remains uncertain.

Porphyria cutanea tarda complicating transfusion-dependent myelodysplastic syndrome

An 83-year-old man presented to our Dermatology department with bullous lesions on the dorsal surface of his hands. He had been diagnosed with myelodysplastic syndrome 8 years previously, and was receiving regular blood transfusions. He was otherwise well, had no history of liver disease, and was teetotal. A random urine sample fluoresced under Wood’s light, and revealed a total porphyrin level of 1260 nmol/mmol creatinine (normal <35 nmol/mmol). Further urinalysis demonstrated a defect at the level of the uroporphyrinogen decarboxylase (UROD) enzyme, confirming the clinical diagnosis of porphyria cutanea tarda. Skin biopsy findings were concordant. Liver function tests were normal, while the ferritin level was grossly raised (5745 lg/l, normal 15–350 lg/l). He was treated with twice weekly oral chloroquine, and advised to avoid sunlight. Darbepoetin was introduced to minimise the need for further transfusions. Resolution of skin blistering was achieved within 3 months. Porphyria cutanea tarda is the most common porphyria, characterised by deficiency of the enzyme UROD. It is acquired in 75% of cases, in which UROD inactivation is restricted to hepatocytes, and mediated by reactive oxygen species in the presence of excess iron. Reduction of UROD activity to a critical point leads to the accumulation of porphyrins, which diffuse out of the plasma, and generate a phototoxic reaction in the upper dermis of sun-exposed skin. Causes include iatrogenic iron overload, haemochromatosis, excess alcohol consumption and infection with hepatitis C virus. Patients present with tense bullae or erosions, typically affecting the dorsal surface of the hands and forearms, as well as the face and scalp. Skin fragility with minor trauma is a common complaint. The blisters are subepidermal, and often heal with scarring, milia and pigmentary changes. Hypertrichosis and sclerotic plaques may develop in chronic, untreated cases. Investigations include examination of urine or faeces for excess porphyrins, skin biopsy, and a screen for potential causes. Phlebotomy is the treatment of choice for patients with a heavy iron burden. Patients for whom this is not appropriate, as in our case, may benefit from treatment with (hydroxy)chloroquine or deferoxamine. Sunlight and alcohol avoidance are crucial for all.