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A 61-year-old Caucasian woman presented with a 4-day history of an acute blistering rash over her arms and legs. She had also developed swelling and puffiness around her eyes with associated vomiting and fever. She had been completely well up to 4 days prior to presentation. Her only medication was bendrofluazide 2.5 mg daily for her long-standing hypertension. She had never smoked and reported no previous skin conditions, allergies or recent travel.
On examination, she looked unwell and was pyrexial at 38.3°C. She had bilateral peri-orbital oedema and palpable supraclavicular lymph nodes. There were raised tender erythematous plaques, associated with tense blisters on some lesions, on her legs (figure 1), arms and face. Larger bullae were found on her forearms and upper back (figure2). There were no nail changes or oral lesions. She had a regular tachycardia of 100 beats/min and a blood pressure of 120/60 mmHg. The rest of the examination was unremarkable.
Investigations showed a haemoglobin of 10.9 g/dl, a white cell count of 15.9 × 109/l (neutrophils 85%), an erythrocyte sedimentation rate (ESR) of 81 mm/h and a C-reactive protein of 132 mg/l. Her throat and skin swabs and blood cultures were negative. Her chest X-ray (figure 3) revealed bilateral hilar lymphadenopathy.
- What is the most likely dermatological diagnosis? Give possible differential diagnoses.
- What are the recognised associations?
- How would you confirm the underlying diagnosis?
The most likely dermatological diagnosis is an acute febrile neutrophilic dermatosis (Sweet's syndrome). The differential diagnoses include erythema multiforme, bullous pyoderma gangrenosum and bullous pemphigoid. In early non-blistering presentations, systemic lupus erythematosus would be an important differential diagnosis. In this case, a skin biopsy showed the typical features of Sweet's syndrome. There was a massive band-like infiltrate in the mid-dermis with numerous neutrophils. The infiltrate was predominantly peri-vascular with no significant leukocytoclastic vasculitis.
Approximately 25% of cases of Sweet's syndrome are associated with para-inflammatory or paraneoplastic disorders.1 About 2% of cases are associated with pregnancy.1 Examples of the recognised associations with Sweet's syndrome are given in boxFB1.1-8
The severity of the cutaneous lesions of the presenting Sweet's syndrome and the patient's age and anaemia (see Discussion) point towards a possible associated malignancy. In view of the history, palpable lymph nodes and bilateral hilar lymphadenopathy, Hodgkin's lymphoma is the probable underlying diagnosis. The differential diagnosis includes bronchogenic carcinoma, pulmonary tuberculosis and sarcoidosis. A lymph node biopsy is therefore the most useful confirmatory investigation followed by computed tomography (CT) of the thorax.
The patient was initially treated with intravenous broad-spectrum antibiotics and prednisolone 60 mg daily. She became apyrexial over the next 4 days and her skin lesions resolved over the next 2 weeks. Hodgkin's lymphoma was confirmed on her lymph node biopsy. CT scan showed stage II disease and she had a good response to her subsequent treatment with radiotherapy.
Acute febrile neutrophilic dermatosis was first described in 1964 by Robert Douglas Sweet from the observation of the condition in eight female patients.2 This disease was subsequently termed Sweet's syndrome. Data on the incidence and prevalence of Sweet's syndrome is limited. A recent retrospective review by Bourkeet al of six dermatological units in the UK revealed only 87 histologically proven cases in total.3The pathogenesis of Sweet's syndrome has yet to be completely elucidated but it is generally accepted to be an immune-mediated reaction. Classically, it occurs in middle aged women after a non-specific infection. It usually presents as a sudden eruption of tender erythematous plaques or nodules on the face, neck and extremities. Vesicobullous lesions occur less commonly.4The onset of the rash is often associated with fever, a raised ESR and neutrophil leucocytosis.1-7 Arthritis or arthralgia and ophthalmic involvement can occur but lymphadenopathy is not a regular feature. The skin lesions often respond well to high-dose systemic corticosteroid therapy1-7 and usually heal without scarring.5 Alternative treatments include potassium iodide, tetracycline and immunosuppressive drugs.1 5Sweet's syndrome recurs in about a quarter of cases.1
At least 10–20% of published cases of Sweet's syndrome occurred in patients with associated malignancy.1 3-7 The onset of Sweet's syndrome tends to coincide with or precede (up to 1 year) the diagnosis of malignancy in more than 60% of these patients.4 They are more likely to be older and to have severe cutaneous lesions and an anaemia.3 4 Recognition of these various presentations of Sweet's syndrome is useful in the light of its potentially serious associations.
Sweet's syndrome associated with Hodgkin's lymphoma.