Vesicular Sézary syndrome with bullous lesions on the feet

ARTICLE

Auteur(s) : Luis Dehesa¹, Jesús Bastida¹, Rafael Camacho-Galán², Conrado Campos-Adsuar³, Javier Gómez-Duaso¹, Jaime Vilar-Alejo¹

¹Service of Dermatology, University Hospital Doctor Negrín, Barranco de la Ballena s.n., 35010 Las Palmas de Gran canaria, Spain
²Department of Pathology, University Hospital Doctor Negrín, Barranco de la Ballena s.n., 35010 Las Palmas de Gran canaria, Spain
³Service of Hematology, University Hospital Doctor Negrín, Barranco de la Ballena s.n., 35010 Las Palmas de Gran canaria, Spain

Vesiculobullous Sézary syndrome (SS) is exceedingly rare. Only 4 cases have been reported until now [1-4]. We report a case of vesicular SS with bullous lesions on the feet.

An 80-year-old woman had been diagnosed as having “pruritus sine materiae” in another medical centre and treated with oral corticosteroids, antihistamines and tricyclic antidepressants without relief. Four months later, she presented in our clinic with exfoliative erythroderma, dyspnea, leg edema and fever for the last two months.

Physical examination showed desquamative erythroderma without mucosal involvement (figure 1A). In some areas, such as forearms, legs, abdomen and feet, desquamation was more intense with crusts (figure 1B). Occasional bullae were seen on the heel and the interdigital folds (figures 1C,D). The patient had axillary, inguinal and cervical lymphadenopathy, but no hepatosplenomegaly.

Cutaneous biopsies from the left forearm showed a band-like lymphocytic infiltrate with massive epidermotropism that formed Pautrier’s microabscesses and multiple intraepidermal vesicles (figures 2A,B). Confluence of vesicles by intervesicular septal rupture was also found (figure 2C). The infiltrate was composed of small and medium lymphocytes with hyperchromatic and cerebriform nuclei (Lützner cells) (figure 2D). These cells were also observed filling intraepidermal vesicles (figure 2E). Immunophenotyping of the infiltrate showed CD2, CD3, CD4, CD5 and CD43 positivity but was negative for CD8, CD20 and FoxP3. Focal expression of CD30 was detected as well, but in less than 5% of lymphocytes. Direct immunofluorescence(DIF) and indirect immunofluorescence (IIF) were negative. Biopsy of a cervical lymph node disclosed nodal infiltration by phenotypically identical cells. The rearrangement of TCR gamma I gene revealed a monoclonal peak, both in nodal and skin samples.

Complete blood cell count showed leukocytosis (16,400 mg/dL) and eosinophilia (14%). More than 25% of circulating cells were atypical medium sized lymphocytes that showed round nuclei, lax chromatin, multiple nucleoli and basophilic vacuolar cytoplasm. In addition, some lymphocytes with cerebriform nuclei were also observed. These cells expressed CD3 (91%), CD4 (99%), CD5 (47%), CD7 (47%) and TCR alpha/beta (98%). Less than 1% of cells expressed CD8. The CD4 to CD8 ratio was 99%. Furthermore, CD16, CD19, CD34, CD56, CD57, TCR gamma/delta, Tdt and Cd1a were negative. Other pertinent features of the blood tests were low level of total protein (49 g/L; Normal: 64-83) and albumin (26,12 g/L; N: 36-50) and raised levels of Beta 2 microglobulin (4,94 ug/mL; N: 0-2,5).

Cultures for bacteria, viruses and fungi were negative except for an occasional growth of Staphylococcus aureus in the interdigital lesions. A short course of oral and topical antibiotics did not change the clinical picture of these lesions but did result in negative cultures. Serological determinations of antibodies against HIV, EBV, CMV and HTLV-1 were negative. Patch testing was also negative. Total body CT studies demonstrated enlarged cervical, supraclavicular, axillary and inguinal lymph nodes without visceral involvement.

In the view of the clinicopathological features we established the diagnosis of vesiculobullous SS. The patient started treatment with 5 day cycles of intravenous cyclophosphamide 750 mg/m² (day 1), intravenous vincristine 1,2 mg/m² (day 1) and oral prednisone 60 mg (days 1 to 5) repeated every 21 days. oui eForty-five days after starting this treatment she died as a consequence of multiorgan failure secondary to a respiratory infection and sepsis in spite of systemic antibiotic treatment.

Differential diagnosis of vesiculobullous SS includes other rare forms of T-cell lymphoma, mainly HTLV-1 virus related adult T cell lymphoma/leukemia (ATLL). This type of lymphoma may present with vesiculobullous cutaneous lesions indistinguishable from MF/SS [6]. Our geographic area is not endemic to ATLL and in our patient HTLV-1 antibodies were negative.

The exact mechanism of vesicle and blister formation in mycosis fungoides and SS is not clear and multiple explanations have been proposed [5]. In our case, we ruled out the coexistence of other blistering diseases such as autoimmune bullous disease and viral or bacterial infections by clinicopathological features, DIF and IIF, and negative cultures. Patch testing was also negative, although in the context of our patient with erythroderma affecting almost one hundred percent of her body surface and being treated with systemic corticosteroids, we can not rule out a false negative result. The clinicopathological features in our patient suggested that massive epidermotropism with formation of Pautrier’s microabscesses led to the formation of vesicles that enlarged by ruptures of intervesicular septae. However, in this case, frank bullae were present only on the feet, suggesting the influence of additional local factors in their formation. Lower extremity edema caused by a decreased level of albumin and some degree of congestive heart failure could play a role in the formation of these bullous lesions. In addition, the heel blister was in a common location for decubitus ulcers and friction forces acting on a previously weakened epidermis by the vesicle formation could cause this presentation. Interdigital bullae were more difficult to explain. Fungal and bacterial cultures of interdigital areas were negative except for an occasional growth of Staphylococcus aureus that was interpreted as colonization because a short course of oral and topic antibiotics was not helpful but cultures became negative. In spite of this we could not rule out an occult tinea pedis or a distant id reaction on previously altered skin causing the interdigital lesions. Accordingly, we consider this case as a peculiar presentation of SS due to the massive epidermotropism of the infiltrate. However, we cannot rule out the action of local factors in the formation of bullous lesions on the feet and prefer to name our case ‘vesicular SS with bullous lesions on the feet’ instead of ‘vesiculobullous SS’.

In our opinion, only one of the four cases of vesiculobullous SS reported until now fulfils the current strict criteria proposed for the diagnosis of this disease [1, 5]. The other 3 cases may be best classified as bullous mycosis fungoides with leukemization [2-5]. Our case might be the second one that fulfils the criteria.

References

2 Betlloch-Mas I, Ramon-Quiles D, Jordá-Cuevas E, Valcuende-Cavero A, Castells-Rodellas A. Síndrome de Sézary Bulleux. Ann Dermatol Venereol 1985; 112: 825-9.

3 Zina G, Bernengo MG, Zina AM. Bullous Sézary syndrome. Dermatologica 1981; 163: 25-33.

4 Aractingi S, Robert C, Reygagne P, Verola O, Dubertret L. Sézary syndrome with palmoplantar bullous lesions. Ann Dermatol Venereol 1992; 119: 894-7.

5 Kazakov DV, Burg G, Kempf W. Clinicopathological spectrum of mycosis fungoides. J Eur Acad Dermatol Venereol 2004; 18: 397-415.

6 Michael EJ, Shaffer JJ, Collins HE, Grossman ME. Bullous adult T-cell lymphoma/leukemia and human T-cell lymphotropic virus-1 associated myelopathy in a 60-year-old man. J Am Acad Dermatol 2002; 46: S137-S141.