On 4 January 2000, a 76 year old man presented to hospital after having experienced a one week history of high fever (ranging from 39°C to 40°C), vomiting, and skin eruptions. Directly before these symptoms occurred, he suffered an unknown fever lasting four weeks. He had been treated for idiopathic thrombocytosis for over three years without symptoms.
A physical cutaneous examination revealed scattered erythematous, purpuric papular, and vesicobullous lesions on his trunk, face, and extremities. The lesions were round and varied from 1 to 2 cm in diameter. Some bulla and pustules were covered with haemorrhagic and necrotic crusts.
The biopsy of a cutaneous lesion on his trunk showed a relatively well demarcated lesion: a mild acanthosis and subcorneal small necrotic bullous lesion with haemosiderin pigmentation (fig 1A). The basal cell layer showed nuclei of various sizes with a pronounced subepidermal infiltrate of lymphocytes (fig 1B). Immunohistochemical analysis (for CD3, CD20, and CD79a) revealed that the infiltrating lymphocytes were predominantly T cells.
Figure 1 (A) Mild acanthosis and subcorneal small necrotic bullous lesions with pronounced subepidermal lymphocyte infiltrates (haematoxylin and eosin stained; original magnification, ×60). (B) The basal cell layer showed nuclei of various sizes with a (more ...)
According to McCarthy et al
we assessed the monoclonality of the infiltrating cells by PCR amplification of the rearranged T cell receptor β (TCRβ) gene using DNA extracted from formalin fixed, paraffin wax embedded sections as a template. In this method, the rearranged V-D-J portion of the TCRβ gene is amplified using several primer pairs selected from three forward primers—V, D1, or D2—and two reverse primers—J1 or J2. Each template was amplified separately with four different primer pairs—V/J1, V/J2, D1/J2, or D2/J2. The PCR conditions and the composition of the reaction mixtures were the same as described previously.5
In each experiment, templates from a cutaneous lymphoma and granulation tissue were included as controls for monoclonality and polyclonality, respectively.
The PCR result with the primer pairs D1/J2 and D2/J2 showed a distinct band of the same size (fig 2, lane 3), whereas amplification with V/J1 or V/J2 showed a smear similar to the polyclonal control.
Figure 2 Polymerase chain reaction with the primer pairs D1/J2 shows a discrete amplified band (lane 3). A cutaneous T cell lymphoma shows a single amplified band (lane 1). A broad smear is amplified from granulation tissue (lane 2). No recognisable band is seen (more ...)
Laboratory studies revealed raised C reactive protein (186 mg/litre) and a mild increase in lactate dehydrogenase. Treponema pallidum haemagglutinin test, hepatitis B surface antigen tests, and blood cultures for bacteria and fungi were negative. These clinical and histological findings suggested a diagnosis of FUMHD.
Ten days of treatment with the antibiotics pentocilin and sulperazon resulted in an improvement in the skin lesions and had a slight effect on the patient’s general condition by eliminating fever. However, on January 15, the patient suddenly developed hypovolaemic shock. After receiving a transfusion he recovered, but became increasingly weak, with a high fever. However, there were no relapsing skin eruptions. Chest x ray revealed ground glass opacity, and laboratory studies revealed raised white blood cell counts (9800–16 100/mm3) and liver enzymes, including lactate dehydrogenase (762 to 1044 IU/litre). He was treated with sulperazon and minocycline, but died 10 days later. No necropsy was performed.
Take home messages
- We report an adult case of febrile ulceronecrotic Mucha–Habermann disease (FUMHD) with a fatal outcome
- This disease is a rare, febrile variant type of pityriasis lichenoides et varioliformis acuta, characterised by necrotic cutaneous ulcerations associated with high fever and systemic manifestations
- The infiltrating cells of the skin lesions were monoclonal in origin and were from an aberrant clone, which may be responsible for host responses, resulting in the severe symptoms observed in this disorder
- Although FUMHD can occur in both adults and children, all cases resulting in fatality are of the adult type (as in our patient), whereas no fatal cases have been reported among children