Long-term remission of recurrent herpes labialis following topical imiquimod application on distant healthy skin: a clinical and immunological study.

BACKGROUND: Given the limitations of current antiviral therapies, safer and more effective approaches to the management of recurrent herpes labialis (RHL) are needed. METHODS: A patient with a 23-year history of RHL and 14 healthy individuals were studied. The patient applied imiquimod to distant healthy skin for 3 weeks. Peripheral blood (PB) samples were collected from the patient during treatment and 21 months after its discontinuation; samples were collected from the controls once. The distribution of lymphocyte populations in PB were analysed by flow cytometry and PB cytokine levels were measured using cytometric bead arrays. RESULTS: The patient showed long-term remission of the disorder subsequent to a 3-week imiquimod application to distant healthy skin. Imiquimod treatment induced the activation and proliferation of T-helper and cytotoxic T-cells, B-cells and T-regulatory cells. In addition, there was a very strong transient increase of T-helper 1 cells (resulting in interferon-γ secretion) and type 1 (pro-inflammatory) polarization of the immune response accompanied by a sustainable interferon-α production. At follow-up 21 months after treatment cessation, with the patient remaining relapse-free, the patient had control levels of all cytokines, increased levels of activated cytotoxic T-cells, continuous production of new T-helper cells and B-cells and near-to-normal levels of T-regulatory cells. CONCLUSIONS: Our results indicate that topical application of imiquimod to healthy skin is capable of causing systemic immunomodulation. This treatment might represent a new and effective alternative to established therapeutic and prophylactic regimens for RHL.

Topical application of imiquimod induces alterations in peripheral blood lymphocytes in healthy individuals.

The aim of this study was to determine whether imiquimod, a Toll-like receptor-7/8 agonist, in addition to its well-known topical action on the cutaneous immune response, might also induce alterations in the peripheral blood lymphocytes. A 62.5 mg quantity of imiquimod (5% cream) was applied topically under occlusion once daily every second day for 3 weeks to the skin of 10 healthy volunteers, age range 30-57 years. Ten sex- and age-matched healthy controls applied corresponding quantities of the vehicle under occlusion. Before, and one and 3 weeks after the start of treatment, peripheral blood lymphocyte subpopulations were measured by flow cytometry. Statistically significant alterations in the percentage or absolute numbers of peripheral blood lymphocyte subpopulations were found in the imiquimod-treated group compared with the control group. These alterations indicate for the first time that topical application of imiquimod induces alterations in peripheral blood lymphocyte subsets in healthy individuals, which may be of importance in the immunotherapy of neoplastic and infectious disorders and should be taken into careful consideration in patients who are treated with imiquimod.

Epileptic seizures as the sole manifestation of neuro-Behçet's disease: complete control under interferon-alpha treatment.

Behçet's disease (BD) is a multisystemic disease of unknown etiopathogenesis with various clinical features including manifestations from central nervous system involvement. We report the case of a patient presented with a 20-year history of BD and a 10-year history of epileptic seizures refractory to various antiepileptic drugs. Under systemic treatment with interferon-alpha 2a (IFN-alpha) a complete remission of the cutaneous manifestations and a seizure-free state were achieved. The impressive therapeutic response of both the seizures and the non-neurological manifestations to IFN-alpha was also observed upon re-administration of this cytokine subsequent to a severe BD relapse. In view of this response and the lack of any other obvious etiology of the seizures in our patient, it seems reasonable to consider them as being the sole manifestation of neuro-BD. The patient is presently completing a 40-month seizure-free follow-up, despite withdrawal of all antiepileptic drugs for the last 35 months. Further studies on large numbers of patients are now warranted to define the therapeutic efficacy and safety of IFN-alpha in neuro-BD and particularly in neuro-BD-related epileptic seizures.

Reduced expression of the antiapoptotic proteins of Bcl-2 gene family in the lesional epidermis of patients with Darier's disease.

BACKGROUND: Dyskeratotic cells in Darier's disease (DD) are thought to represent apoptotic keratinocytes. Bcl-2 gene family proteins play a major role in the regulation of apoptosis of epidermal keratinocytes and reveal pleiotropic interactions with intracellular Ca2+ homeostasis. The latter is impaired in DD because of mutations of ATP2A2 gene that encodes the type 2 isoforms of the sarcoplasmic/endoplasmic reticulum (ER) Ca++ ATPase 2 (SERCA2) pump. METHODS: The expression of Bcl-2, Bax, and Bcl-x(L) proteins was investigated in the epidermis of 11 patients with DD and of 11 sex- and age-matched healthy controls by immunohistochemistry. RESULTS: The expression of Bcl-2 and Bcl-xL was clearly reduced in the lesional epidermis of the patients, as compared with the normal epidermis of healthy controls, whereas the expression of Bax remained unaltered. CONCLUSIONS: The alterations in the expression of Bcl-2 gene family proteins could be a crucial event for the activation of the apoptotic process in the lesional epidermis of DD patients and for the occurrence of the characteristic dyskeratotic keratinocytes. The question as to whether these alterations are associated with the ER Ca2+ depletion in DD or represent secondary phenomena unrelated to the genetic defect of this genodermatosis remains to be elucidated.

Short-term oral isotretinoin therapy does not cause clinical or subclinical peripheral neuropathy.

BACKGROUND: Subclinical neurophysiologic abnormalities mainly suggestive of sensory fibers dysfunction were observed in some patients after 1 and 3 months of treatment with oral acitretin. Moreover, two cases of peripheral sensory neuropathy and one of sensorimotor polyneuropathy were observed after short-term oral administration of this compound. OBJECTIVE: The objective of this prospective study was to investigate whether short-term treatment with oral isotretinoin can also affect peripheral nerve function. METHODS: Serial neurologic and neurophysiologic examinations were performed on 18 young patients with severe nodulocystic acne prior to and 1 and 3 months after the onset of oral isotretinoin treatment (1 mg/kg per day). RESULTS: Clinical neurologic examination before and under treatment disclosed no abnormalities in any of the patients. There were no significant differences between the pre- and post-treatment neurophysiologic parameters. Furthermore, evaluation of the serial neurophysiologic measurements in each patient separately under oral isotretinoin treatment revealed no changes fulfilling the criteria of abnormality. CONCLUSIONS: Short-term administration of oral isotretinoin in young patients does not cause clinical or subclinical neuropathy.

Ehlers-Danlos type IV syndrome in a patient with Down syndrome: simple co-occurrence or true association?

Down syndrome, a common chromosome aneuploidy, has been associated with an increased incidence of cutaneous disorders. The simultaneous occurrence with Ehlers-Danlos syndrome (EDS) is rare. We report here the clinical case of a 19-year-old female patient with Down syndrome (trisomy 21) who was also affected by EDS type IV. She died from spontaneous bleeding due to rupture of nonaneurysmal abdominal aorta. Since the affected chromosomes in these two syndromes are different (21 and 2, respectively), the concomitant appearance of Down syndrome and EDS type IV in our patient, though clinically intriguing, most likely represents a co-occurrence. However, the possibility that a presently unknown link may exist between these syndromes cannot be ruled out.

Hsp27 expression coincides with epidermal stratification during human epidermal morphogenesis.

Heat shock protein 27 (Hsp27), apart from its protective function in response to stress, is implicated in the regulation of cell growth, differentiation and apoptosis. Data on the expression of Hsp27 in the developing human epidermis are sparse and partially conflicting. Thus, the purpose of the present study was to investigate Hsp27 expression during the morphogenesis of human epidermis. Skin biopsies and dispase-separated epidermal sheets obtained from 7 human embryos (7 and 8 weeks estimated gestational age, EGA), from 79 human fetuses (9-23 weeks EGA) and from 10 healthy adult volunteers were investigated by immunohistochemistry and Western blotting, respectively. The earliest detection of Hsp27 expression was found by immunohistochemistry at the 12th week EGA (basal and intermediate layer) and by Western blotting at the 9th week EGA. From the 16th to the 23rd week EGA immunoreactivity was not detectable in the basal layer, whereas in the overlying layers it revealed a differentiation-related pattern. The simultaneous onset of epidermal stratification and Hsp27 expression (9th week EGA) and the alterations of the latter in the subsequent stages of development, suggest that this stress protein may be involved in the molecular events underlying human epidermal morphogenesis.

Short stature, type E brachydactyly, exostoses, gynecomastia, and cryptorchidism in a patient with 47,XYY/45,X/46,XY mosaicism.

We report a 72-year-old male patient with a 47,XYY/45,X/46,XY mosaicism associated with short stature, exostoses, type E brachydactyly, gynecomastia, cryptorchidism, mild mental retardation, and a paranoid personality and conversion disorder. Since his prevalent cell line was 47,XYY (about 75%), our patient could be karyotypically classified as a case of 47,XYY syndrome. In view of the striking similarity of the clinical features of this case and those of a XYY case previously reported by Ikegawa et al (1992), it seems reasonable to suggest that these patients are representatives of a novel syndrome with a XYY karyotype.

Anaphylactic shock as the only clinical manifestation of hepatic hydatid disease.

The case of a 35-year-old man is reported who developed a spontaneous anaphylactic shock as the only clinical manifestation of hepatic hydatidosis. Dermatologists should consider asymptomatic hydatid disease in the differential diagnosis of anaphylactic reactions, particularly in patients from regions in which echinococcosis is endemic.

Enzyme replacement therapy in severe Fabry disease with renal failure: a 1-year follow-up.

We present here the course of clinical response of a 53-year-old haemodialysed Fabry patient who received recombinant human alpha-galactosidase A at a dose of 1 mg/kg every other week over a period of 1 year. The therapy was well tolerated by the patient, who revealed an impressive favourable cutaneous, gastrointestinal, neurological and psychiatric response and a dramatic improvement in his quality of life, but no improvement in cardiac and renal function.