Adverse reactions during biological drug therapy in psoriasis:clinical series and a review of the literature.

AIM: Psoriasis is a chronic, inflammatory skin disorder, histologically characterized by epidermal hyperplasia, anomalous keratinocyte differentiation, angiogenesis, and by inflammatory cell infiltrate. Psoriasis has a significant impact on quality of life and is often associated with serious psychological effects. The use of biological agents is expanding worldwide as alternative treatment for chronic inflammatory diseases including psoriasis. The European Medicines Agency (EMEA) approved the use of Efalizumab, Etanercept, Infliximab and Adalimumab in the treatment of psoriasis on the basis of the positive findings obtained from well-designed clinical trials. The ongoing monitoring of tolerability and possible side-effects of these drugs has, however, recently lead to the EMEA suspending Efalizumab on the grounds that the possible risks of its use outweighed the benefits. METHODS: Fifty-four patients treated with the two classes of biological drug (Efalizumab and anti-TNF-α) were studied. The choice of biological drug therapy was conditioned by the extent and seriousness of the disease and by the presence of concomitant pathologies. RESULTS: Nineteen patients presented adverse reactions, of which 9 necessitated interruption in treatment (6 Efalizumab and 3 anti-TNF-α). CONCLUSION: This work reports the adverse reactions to these biological therapies found in our patients along with a review of the literature concerning adverse reactions in psoriasis treatment. From our experience and basing ourselves on the literature reporting studies conducted in large centres, we feel that it is indispensable to continue monitoring any reactions during biological drug treatment. In this way, there is more likelihood of preventing, where possible, or better managing any reactions linked to the use of these drugs.

Cutaneous sporotrichoid leishmaniasis resistant to pentavalent antimonial therapy: complete resolution with itraconazole.

Sporotrichoid leishmaniasis is a sporadic form of cutaneous leishmaniasis, a protozoal infection, reported particularly in the Middle East. Clinically it occurs as nontender, subcutaneous, slightly erythematous nodules, often associated with lymphangitis, usually on exposed areas of the skin. Sometimes it occurs after treatment with a single dose of antimonials, and in older lesions, the biopsy can be negative for amastigotes. We report a case of cutaneous sporotrichoid leishmaniasis unresponsive to intralesional pentavalent antimonial therapy, which completely resolved after treatment with oral itraconazole. To our knowledge, this is only the third such case reported. We discuss the causes of dissemination of the nodular lesions and the negative results for amastigotes on re-biopsed lesions.

Chemotherapy-induced persistent serpentine supra-venous hyperpigmented eruption and persistent supra-venous erythematous eruption: case report.

This paper presents the case of an 85-year-old male affected by classic Kaposi's sarcoma (CKS) since 1994. The disease was widespread over much of the skin surface. Since 1995 the patient had undergone several chemotherapy treatments with good, but not lasting results. Due to a worsening in the pathology, in October 2005 the patient was prescribed a further cycle of vinorelbine. Twenty-four hours after the first infusion, followed by isotonic sodium chloride solution vein wash, a supra-venous serpentine erythematous lesion appeared directly above infusion site. The lesion extended centripetally from the injection point and involved the whole supra-venous area. Over the following days, a gradual variation in lesion colour, from erythematous to hyperpigmented, was observed. Given this clinical and histological picture, the diagnosis of persistent serpentine supra-venous hyperpigmented eruption (PSSHE) was made. Draft of a rare secondary effect whose pathogenesis still remain to explain. The literature holds reports of another skin manifestation with similar supra-venous characteristics: persistent supra-venous erythematous eruption (PSSE), clinical entity that enters in differential diagnosis with the PSSHE. Many of the drugs used in chemotherapy have been indicated as responsible for these peculiar side-effects. To the authors' knowledge, the literature reports only one PHSSE case induced by i.v. vinorelbine infusion.

A psoriasis vulgaris protective gene maps close to the HLA-C locus on the EH18.2-extended haplotype.

We determined the molecular haplotypes of the HLA-A, HLA-C and HLA-B loci and the MHC class I-B-related (MIB) microsatellite in 179 unrelated psoriatic patients (72 familial cases) and in 120 controls. The HLA-A*3002-Cw*0501-B*1801-MIB1 haplotype showed a strong negative association with psoriasis vulgaris (PV) and in particular with familial PV, revealing the presence of a PV-protective gene. Analysis of association and linkage disequilibrium of the single alleles and the various two-three-four-locus segments of this haplotype indicated the presence of a protective gene telomeric to the HLA-C locus. This finding was confirmed in 13 informative multiplex PV families, in which at least one parent carried the EH18.2 haplotype. In two families, an affected sibling presented HLA-A/C recombination on the EH18.2 haplotype. A study of 12 polymorphic microsatellites in all members of the informative families, 145 PV patients, 120 controls and 32 EH18.2 homozygous healthy individuals demonstrated that the protection conferred by the EH18.2 haplotype lies within a 170 kb interval between the C143 and C244 loci, most probably in a 60 kb segment between the C132 and C244 loci.

Sjögren's syndrome: a retrospective review of the cutaneous features of 93 patients by the Italian Group of Immunodermatology.

OBJECTIVE: Various cutaneous manifestations have been described (xerosis, eyelid dermatitis, angular cheilitis, cutaneous vasculitis and annular erythema) in Sjögren's syndrome (SS), but so far only three studies on large numbers of SS patients have been carried out. The frequency of cutaneous manifestations and their association with specific clinical or immunological parameters have never been studied. The aim of the Italian Group of Immunodermatology was to evaluate these associations in a large number of SS patients. METHODS: A retrospective review was performed on 93 patients with SS followed over a ten-year period (1990-2000) at 6 Italian dermatological centers. They were subdivided into two groups, 62 with primary SS and 31 with secondary SS, and the frequency of cutaneous manifestations and specific antibodies was determined and compared between them. RESULTS: We found significantly higher levels of xerosis (p = 0.009) (56.4% versus 25.8%) and angular cheilitis (p = 0.017) (38.7% versus 16.1%) in primary SS patients than in those with secondary SS. A significant association of xerosis with anti-SSA + SSB (p = 0.033) antibodies was also demonstrated. Eyelid dermatitis and pruritus were common but less specific cutaneous symptoms. Annular erythema was found more often in primary (6.45%) than in secondary (3.2%) SS and was associated with SSA + SSB antibodies in 75% of the cases. Cutaneous vasculitis was present in 30.6% of primary SS (manifesting as palpable purpura in 84%) and in 29.3% of secondary SS cases. CONCLUSION: Xerosis is the most frequent and characteristic cutaneous manifestation of primary SS. It is not linked to decreased sebaceous or sweat gland secretion, but more probably to a specific alteration of the protective function of the stratum corneum. Angular cheilitis is a common but less specific skin lesion in SS and is associated with xerosis and xerostomia.

Usefulness of 99mTc-tetrofosmin scintigraphy in different variants of Kaposi's sarcoma.

We investigated (99m)Tc-tetrofosmin scintigraphy in 27 patients with Kaposi's sarcoma: 20 had classic (CK), 5 AIDS-associated (AK) and 2 transplantation-associated (TK) variants. Twenty-three patients had clinically evident cutaneous and/or mucosal lesions, 9 of them with associated sarcomatous lymphadenopathy; 2 TK patients had only lymph nodes or other extracutaneous Kaposi sites. Both planar and SPECT (99m)Tc-tetrofosmin scintigraphies were performed in all cases and neck pinhole (P)-SPECT in selected patients. (99m)Tc-tetrofosmin uptake was observed in 88% of patients with clinically evident cutaneous and/or extracutaneous Kaposi lesions. Scintigraphy gave additional information on cutaneous lesion extent, particularly SPECT regarding deep invasion and subclinical sites in some cases. However, scintigraphy was less sensitive in the detection of small, isolated and scattered lesions. SPECT/P-SPECT were positive in 8/8 patients with sarcomatous lymph nodes, planar imaging in 5/8, ultrasonography in 7/8, while all procedures were negative in 6 other patients with reactive or HIV infection lymph nodes. SPECT demonstrated lymphadenopathy remission in 1 TK patient after immunosuppressive therapy modification and, like planar imaging, ascertained an associated lymphoma with (67)Ga-citrate combined. (99m)Tc-tetrofosmin scintigraphy, especially SPECT, can be useful both in the detection and staging of Kaposi sarcoma lesions as a complementary tool to clinical and other conventional diagnostic methods.

Direct correlation between human herpesvirus-8 seroprevalence and classic Kaposi's sarcoma incidence in Northern Sardinia.

The human herpesvirus-8 (HHV-8) has been associated with the development of Kaposi's sarcoma. A high incidence of classic Kaposi's sarcoma has been described in Sardinia, an island West of Italy's mainland. Different seroepidemiological analyses have reported that prevalence of HHV-8 infection varies worldwide: a high HHV-8 seroprevalence has been shown in Italy. The present survey was carried out to evaluate the correlation between HHV-8 infection and classic Kaposi's sarcoma incidence in northern Sardinia. Blood samples were collected from 226 healthy donors born and resident in five different areas of North Sardinia. Seroprevalence to HHV-8 was determined searching antibodies to viral lytic proteins by immunofluorescence in sera diluted at 1:10. Classic Kaposi's sarcoma incidence data spanning a period of 23 years were examined in the areas studied. The present screening revealed that seroprevalence was 35%, within a range of 15.3-46.3% in the five areas, although it should be considered that the seroprevalence to HHV-8 can be established more accurately by the combined use of different assays. Age emerged as an important risk factor. Indeed, subjects aged > 50 years showed a higher seroprevalence to HHV-8 as compared with younger individuals. A strong direct correlation between HHV-8 prevalence and classic Kaposi's sarcoma incidence has been also observed. The wide diffusion of HHV-8 in Sardinia appears to represent an important factor in the high incidence of classic Kaposi's sarcoma reported in the island. However, additional co-factors, such as age, sex, genetic traits, or viral strain pathogenicity, are likely to play a role in the development of the disease.