Agustín España

Skin cancer in heart transplant recipients

BACKGROUND The frequency of skin cancer in organ transplant recipients is high, up to 15%. OBJECTIVE Our purpose was to determine the incidence of skin cancer in patients who underwent immunosuppression after heart transplantation and to determine the factors important in the appearance of skin cancer. METHODS We studied the frequency of skin cancer in 92 of 111 patients after they underwent heart transplantation between January 1984 and December 1993. RESULTS At least one cutaneous neoplasm (squamous cell carcinoma and/or basal cell carcinoma) developed in 14 patients (15.2%). The basal cell carcinoma to squamous cell carcinoma ratio was 1:1.5. The skin cancer appeared an average of 31.5 months after transplantation; the average was 36 months for squamous cell carcinoma and 25.3 months for basal cell carcinoma. Cumulative risk rose from 4.3% at 1 year up to 43.8% at 7 years after transplantation. The overall incidence of both types of skin cancer was 45.3 per 1000 posttransplant person-years, with an incidence of 25.8 for basal cell carcinoma and 29.1 for squamous cell carcinoma. Most skin cancers developed between 2 and 3 years after transplantation. All patients were exposed to a significant amount of ultraviolet radiation and had skin type II or III. We did not find a significant association between skin cancer and haplotype HLA-A3, HLA-A11, HLA-DR, and the number of mismatches for HLA-B. CONCLUSION We found an increased progressive cumulative incidence of skin cancer in heart transplant recipients for two reasons: (1) immunosuppression and increased exposure to ultraviolet radiation in some patients, and (2) the skin type of certain patients. We emphasize the need for photoprotection in this group of patients and regular skin cancer screening examinations.

In vivo blockade of pemphigus vulgaris acantholysis by inhibition of intracellular signal transduction cascades.

Background  Pemphigus vulgaris (PV) is an autoimmune disease characterized by mucocutaneous intraepithelial blisters and pathogenic autoantibodies against desmoglein 3. The mechanism of blister formation in pemphigus has not been defined; however, in vitro data suggest a role for activation of intracellular signalling cascades.

Nonmelanoma skin cancer after liver transplantation. Study of risk factors

Nonmelanoma skin cancer (NMSC) is a frequent complication after liver transplantation, but the risk factors of posttransplant NMSC have not been well defined. In a prospectively followed series of 170 liver transplant recipients, we assessed the incidence of NMSC, compared it with the expected incidence in the general population, and investigated which risk factors were related to NMSC. After a median follow‐up of 62 months, 27 patients developed 43 NMSC. The relative risk of NMSC was 20.26 (95% confidence interval: 14.66‐27.29) as compared with sex‐ and age‐matched population. In univariate analysis, older age, male sex, Child‐Turcotte‐Pugh A or B at transplantation, treatment with mycophenolate mofetil, skin type, and total pretransplant sun burden were associated to the development of NMSC. In multivariate analysis, only skin type and total sun burden were independently related to NMSC. In conclusion, risk of posttransplant NMSC may be estimated combining skin type and an easy estimation of total sun burden. No individual immunosuppression regimen seems to be related to a higher risk of NMSC. (Liver Transpl 2005;11:1100–1106.)

Pemphigus vulgaris autoantibodies induce apoptosis in HaCaT keratinocytes.

Pemphigus vulgaris (PV) is an autoimmune disease characterized by binding of IgG autoantibodies to epidermal keratinocyte desmosomes. IgG autoantibodies obtained from a patient with mucocutaneous PV reacted with plakoglobin (Plkg) in addition to desmoglein‐3 (Dsg3) and Dsg1. Immunofluorescence analysis confirmed that IgG autoantibodies, unlike antibodies from a healthy volunteer, caused disruption of cell–cell contacts in HaCaT keratinocytes. Moreover, apoptosis was enhanced in cells treated with autoantibodies compared to those treated with normal antibodies. The apoptotic process induced by IgG autoantibodies was characterized by caspase‐3 activation, Bcl‐2 depletion and Bax expression. The present report demonstrates that PV IgG autoantibodies promote apoptosis in HaCaT keratinocytes.

An imbalance in Akt/mTOR is involved in the apoptotic and acantholytic processes in a mouse model of pemphigus vulgaris

Abstract:  Pemphigus vulgaris (PV) is an autoimmune blistering disease characterized by the presence of IgG autoantibodies against Dsg3. Our aim was to investigate the molecular events implicated in the development and localization of apoptosis and acantholysis in PV. We used a passive transfer mouse model together with immunohistochemical (IHC) techniques and the TUNEL assay, with quantification analysis in the basal layer of the epidermis. The activated signalling molecules analysed and apoptotic cells detected showed an identical localization. Herein, we found for the first time in vivo an increased expression of activated HER receptor isoforms in the basal layer in PV lesions. Besides, we observed the almost total lack of activated Akt compared with a higher level of activated mTOR within the basal cells of the epidermis. Our observations strongly support that the restriction of acantholysis to the basal layer may be due, at least in part, to the selective and increased presence of activated HER receptor isoforms in these cells. After phosphorylation of HER receptor isoforms, intracellular signalling pathways are activated in the basal layer. In addition, the imbalance in Akt/mTOR that takes place in the basal cells may provide intracellular signals necessary for the development of apoptosis and acantholysis.

Cutaneous polyarteritis nodosa

Summary Classic polyarteritis nodosa (PAN) is a segmentary leucocytoclastic vasculitis that affects small‐ and medium‐sized arteries. In 1931, Lindberg (Acta Med Scand 1931; 76: 183–225) described the existence of a cutaneous variant of PAN, without visceral involvement and with a more favourable prognosis. We present four patients diagnosed with cutaneous PAN in our hospital between 1987 and 1998. The study group was composed of three women and one child, whose ages ranged from 11 to 70 years old. The follow‐up period was between 2 and 13 years. Each patient was submitted for an initial clinical, histological and laboratory evaluation and subsequent follow‐up. The presence of nodules was the most frequent cutaneous lesion, preferentially located in the lower limbs. The erythrocyte sedimentation rate was the only parameter that was altered in all patients. Cutaneous biopsies from all patients showed a segmentary leucocytoclastic vasculitis in the arteries of the deep dermis and/or hypodermis. Direct immunofluorescence was positive in just one patient. No visceral involvement was found in any patient. There is confusion about the correct definition of cutaneous PAN. Some clinical findings, such as nodules or livedo reticularis, typical of cutaneous PAN suggest a good prognosis; however, we consider that it is necessary to evaluate these patients for systemic involvement for the possibility of arteritis in other organs as the term polyarteritis suggests.

Graft-versus-host disease after liver transplantation

We describe a case of graft-versus-host disease that developed in the recipient of an orthotopic liver transplant. A maculopapular eruption developed on postoperative day 25. After the diagnosis of graft-versus-host disease was made aggressive therapy was instituted, which resulted in a complete recovery.

Vegetating iododerma with underlying systemic diseases: Report of three cases

Three patients with vegetating iododerma as a result of potassium iodide therapy are presented. The first patient had polyarteritis nodosa, the second had monoclonal gammopathy of undertermined significance, and the third had multiple myeloma. Vegetating iododerma probably represents an idiosyncratic response to iodides; patients with polyarteritis nodosa and paraproteinemias may be predisposed.

Are eosinophilic pustular folliculitis of infancy and infantile acropustulosis the same entity

Summary An infant is described with an overlap picture of eosinophilic pustular folliculitis and infantile acropustulosis.

Chronic Balanitis with Palisading Granuloma: An Atypical Genital Localization of Necrobiosis lipoidica Responsive to Pentoxifylline

We report a case of necrobiosis lipoidica located on the glans penis of a patient without diabetes mellitus. Both clinical and histologic features favor the diagnosis of necrobiosis lipoidica, even though the location is unusual. Treatment with pentoxifylline was effective. The differential diagnosis is discussed.