Mortality and prognostic factors in patients with bullous pemphigoid: a retrospective multicenter Italian study.

INTRODUCTION: Bullous pemphigoid is the most common autoimmune bullous dermatosis. In recent years several studies have tried to identify the main factors of the disease related with an increased risk of death. The aim of this multicenter Italian study was to assess the risk score of death considering epidemiologic, clinical, immunological, and therapeutic factors in a cohort of patients affected by bullous pemphigoid and try to identify the cumulative survival up to 120 months. METHODS: We retrospectively reviewed the medical records of patients with bullous pemphigoid who were diagnosed between 2005 and 2020 in the 12 Italian centers. Data collected included sex, age at the time of diagnosis, laboratory findings, severity of disease, time at death/censoring, treatment, and multimorbidity. RESULTS: A total of 572 patients were included in the study. The crude mortality rate was 20.6%, with an incidence mortality rate of 5.9 × 100 person/year. The mortality rate at 1, 3, 5, and 10 years was 3.2%, 18.2%, 27.4% and 51.9%, respectively. Multivariate model results showed that the risk of death was significantly higher in patients older than 78 years, in presence of multimorbidity, anti-BP180 autoantibodies >72 U/mL, or anti-BP230 > 3 U/mL at diagnosis. The variables jointly included provided an accuracy (Harrel's Index) of 77% for predicting mortality. CONCLUSION: This study represents the first nationwide Italian study to have retrospectively investigated the mortality rates and prognostic factors in patients with bullous pemphigoid. A novel finding emerged in our study is that a risk prediction rule based on simple risk factors (age, multimorbidity, steroid-sparing drugs, prednisone use, and disease severity) jointly considered with two biomarkers routinely measured in clinical practice (anti-BP230 and anti-BP180 autoantibodies) provided about 80% accuracy for predicting mortality in large series of patients with this disease.

Clinical and serological predictors of relapse in pemphigus: a study of 143 patients.

BACKGROUND: Pemphigus is an autoimmune bullous disease mediated by autoantibodies targeting epithelial cell-cell adhesion molecules. Predictors of relapse have not yet been clearly identified. AIMS: To identify factors at diagnosis and during follow-up that could be predictors of relapse. METHODS: Clinical and immunopathological data at diagnosis, clinical remission and first relapse from patients with pemphigus vulgaris or foliaceus and at least a 36-month follow-up were collected retrospectively. Based on the autoantibody profile at diagnosis, three serological patient subsets were devised: (i) anti-desmoglein (Dsg)1-positive and anti-Dsg3-negative; (iii) anti-Dsg1-negative and anti-Dsg3-positive; and (iii) anti-Dsg1-positive and anti-Dsg3-positive. RESULTS: Data from 143 patients were collected. No significant differences were found between relapsers (n = 90) and nonrelapsers (n = 53) for time to remission or for anti-Dsg1 and anti-Dsg3 titres at diagnosis and remission. In the analysis of all patients, a higher risk of relapse was found for a body surface area (BSA) score of 3 compared with BSA < 3 (OR = 3.30, 95% CI 1.17-9.28; P = 0.02) and for a positive titre of either anti-Dsg1 or anti-Dsg3 autoantibodies at remission compared with both being negative (OR = 2.42, 95% CI 1.21-4.85, P = 0.01). In patients who were anti-Dsg3-positive and anti-Dsg1-negative at diagnosis, failure to achieve anti-Dsg3 negativity at clinical remission was a significant predictor of relapse (OR = 7.89, 95% CI 2.06-30.21; P < 0.01). Similarly, failure to achieve anti-Dsg1 negativity at clinical remission was a significant predictor of relapse in patients with both anti-Dsg1 and anti-Dsg3 positivity at diagnosis (OR = 5.74, 95% CI 1.15-28.61; P = 0.03), but not in those who were anti-Dsg1-positive/anti-Dsg3-negative at diagnosis (OR = 1.08, 95% CI 0.27-4.30; P = 0.91). CONCLUSION: Regardless of pemphigus subtype, autoantibody titre negativity at clinical remission in patients classified based on their anti-Dsg1 and anti-Dsg3 profile at diagnosis and BSA were useful tools in predicting relapse.

Thalidomide treatment for hypertrophic cutaneous lupus erythematosus.

INTRODUCTION: In recent years numerous reports have been published regarding satisfactory thalidomide therapy for refractory chronic cutaneous lesions of lupus erythematosus (CCLE); to date, in the literature, there is just one report describing two patients affected by hyperkeratotic CCLE successfully treated with thalidomide. METHODS: Six patients affected by a hypertrophic/verrucous variant of CCLE were treated with thalidomide during the period October 1999 to December 2002 and their medical records were retrospectively reviewed. The initial dose of thalidomide was 100 mg/die by mouth for all the cases, while the duration of therapy was variable among the patients. RESULTS: All six patients responded to treatment: two had partial resolution of the lesions and four achieved almost complete clearing of cutaneous disease. Response to treatment was seen in the first month of therapy in all the patients. Follow-up nerve conduction studies were negative but a patient had to discontinue the drug because of neurological problems. DISCUSSION/CONCLUSION: Our case series confirms the efficacy of a 'low-dose' thalidomide regimen in verrucous/hyperkeratotic CCLE, which is normally unresponsive to conventional treatment; in this setting, thalidomide should be kept in mind as an extremely valid therapeutic option despite the lack of prospective, randomized, double-blind, placebo-controlled studies.

Ultraviolet light exposure is not a requirement for the development of cutaneous neonatal lupus.

Cutaneous neonatal lupus erythematosus (NLE) is a rare disorder, linked to the presence of transplacentally acquired maternal autoantibodies (anti-ENA). NLE skin lesions frequently appear in the second or third month of life, and ultraviolet exposure is thought to be an initiating factor since it can externalize intranuclear autoantigens at the cell surface. We report a baby who was born already with an extensive NLE rash, suggesting that sun exposure is not a requirement for the development of NLE skin lesions. A 31-year-old woman affected with mixed connective tissue disease gave birth to a female after 38 weeks of gestation. Pregnancy was uneventful and no perinatal complications were seen. The mother was positive for anti-RNP, but negative for anti-SSA/Ro and SSB/La autoantibodies. Already at birth, an extensive scarring rash with a few erythematosus lesions was present on the baby's face and scalp; this progressed over the following months, and subsequently stabilized. Anti-RNP were present in the baby's serum. Due to the unusual features of the disease expression, a skin biopsy was performed at age 5 months; results were consistent with the diagnosis of NLE, showing mononuclear cell infiltration and immunoglobulin deposition. No other features of NLE were detected. This observation is unusual for: (1) the presence of an NLE rash in the absence of anti-SSA/Ro; (2) the scarring and atrophic characteristics of the lesions; and (3) the development already in utero. This latter finding argues against sun exposure being necessary for lesion induction.

Shorter survival of SDF1-3'A/3'A homozygotes linked to CD4+ T cell decrease in advanced human immunodeficiency virus type 1 infection.

The SDF-1 3'A allelic polymorphism has been reported to influence either positively or negatively the progression of human immunodeficiency virus type 1 (HIV-1) disease. Therefore, the SDF-1 genotype of 729 HIV-1-infected individuals pooled from 3 distinct cohorts was determined. A statistically nonsignificant association between the SDF1-3'A/3'A genotype and accelerated disease progression was evident among seroconverters (n=319), but a striking correlation of decreased survival after either diagnosis of AIDS according to the 1993 definition or loss of CD4(+) T cell counts <200 was observed. The relative hazards for SDF1-3'A/3'A homozygotes, compared with heterozygotes and wild-type homozygotes were 2.16 (P=.0047), for time from diagnosis according to the 1993 Centers for Disease Control and Prevention AIDS case definition (AIDS-'93) to death, and 3.43 (P=.0001), for time from CD4(+) T cells <200 to death. Because no difference in survival was observed after diagnosis according to AIDS-'87, the association of the SDF1-3'A/3'A genotype with the accelerated progression of late-stage HIV-1 disease appears to be explained for the most part by the loss of CD4(+) T lymphocytes.

Erythema elevatum diutinum and HIV infection: a report of five cases.

Erythema elevatum diutinum (EED) is emerging as a specific HIV-associated dermatosis, 11 cases having so far been reported in the medical literature and five patients with the disease having been seen by us during the last 4 years. As the disease is poorly known, it is easily confused with Kaposi's sarcoma or bacillary angiomatosis, but the histopathological features are diagnostic. EED is considered to be an immune complex-mediated vasculitis. A streptococcal infection seemed to be the trigger factor in four of our patients. Partial control of the cutaneous lesions was achieved by the use of antibiotics.

Disseminated histoplasmosis presenting with cutaneous lesions in a patient with acquired immunodeficiency syndrome.

OBJECTIVE: Presentation of a case of disseminated histoplasmosis, observed in a non-endemic area, in which cutaneous lesions and fever were the dominant clinical signs of the infection. CASE: A 54-year-old homosexual man with acquired immunodeficiency syndrome (AIDS) related Kaposi's sarcoma presented with cutaneous lesions and fever due to disseminated histoplasmosis. The patient was successfully treated with itraconazole 200 mg/day. He died after 8 months from AIDS dementia complex: disseminated histoplasmosis relapse was not observed. CONCLUSION: The case shows that infection with Histoplasma capsulatum must be considered by dermatologists in HIV/AIDS patients, even in non-endemic areas.

Lichen myxoedematosus in a patient with AIDS.

We report a patient with acquired immunodeficiency syndrome (AIDS) who developed a widespread papular eruption due to deposition of mucin in the dermis. Paraproteinaemia was demonstrated. Lichen myxoedematosus type 2 was diagnosed. This is the third case of this rare disorder reported in a human immunodeficiency virus (HIV)-seropositive subject.

Three-year neuropsychological follow-up in a selected group of HIV-infected homosexual/bisexual men.

OBJECTIVE: To evaluate changes in cognition in a selected group of asymptomatic homosexual/bisexual men over a 3-year period. PATIENTS AND METHODS: Sixty HIV-infected (Centers for Disease Control stage II) subjects and 60 controls (individually matched for age and years in education) were administered neuropsychological tests evaluating attention, language, memory, logic and visuo-motor abilities. None of the patients had a history of alcohol or drug abuse, and all received the baseline cognitive evaluation within 18-24 months of seroconversion. RESULTS: The HIV-infected subjects differed from controls in only one of the six memory tests (P < 0.01). Follow-up evaluation after 18 and 36 months (available for 51 and 36 subjects, respectively) demonstrated a significant deterioration in visuo-motor ability (P < 0.01) only in subjects who had progressed to AIDS, without signs or symptoms of central nervous system involvement. CONCLUSIONS: The data suggest that cognitive alterations in asymptomatic stages of HIV infection are in most subjects minor and do not develop. Percentage rates of CD4 lymphocyte decline appear to be significantly related to deterioration in visuo-motor abilities.

Non-pathogenic entamoeba histolytica in Italian HIV-infected homosexuals.

A cohort of 51 homosexuals who were either HIV-positive or had AIDS was followed prospectively with parasitologic stool examination and in vitro culture in order to determine the incidence of E. histolytica infection. Amoebic isolates were further characterized by electrophoretic isoenzyme study. Five subjects (9.8%) were found to be infected with E. histolytica. None of the amoebic isolates were found to be pathogenic by isoenzyme analysis.

Cognitive abnormalities and disease progression in a selected population of asymptomatic HIV-positive subjects.

A selected population of 41 homosexual/bisexual asymptomatic HIV-positive subjects were administered neurophysiological tests to assess language, memory, attention, logic faculties and visuo-motor functions. HIV-positive subjects differed from individually matched control subjects only in certain measures of verbal memory. Longitudinal evaluation performed after 1.5 years, however, did not indicate any further development of this mild amnesic deficit. Despite the small number studied in our sample, there seems to be a trend for older subjects to be at greater risk of developing AIDS and cognitive abnormalities than younger subjects, while differences in immunological status play a significant role in disease progression.

Concomitant syphilitic and HIV infection. A case report.

Evolution of syphilis has been studied in HIV-seropositive patients with regard to progression mode and clinical pictures. Reciprocal interactions between syphilis and HIV have been suggested based on the observation of unusually aggressive forms of treponemic infection, particularly at the CNS level. We describe a case of a 52-year-old homosexual male AIDS presenting with clinically manifest tabe dorsalis. The evolution to neurosyphilis seems, at least in this stage, to be accelerated by superimposed HIV infection.

Oral hairy leukoplakia.

Oral hairy leukoplakia was first described in homosexual men infected with the human immunodeficiency virus. It is thought to be caused by infection with both the Epstein-Barr virus and human papillomavirus. We report 59 cases of oral hairy leukoplakia. The disease was diagnosed in patients in all risk groups and was categorized in all classes of the Walter Reed classification without significant differences in prevalence. Epstein-Barr virus could be demonstrated in all tissue samples examined; human papillomavirus was found in only a few specimens. In our series oral hairy leukoplakia had a chronic course, although temporary spontaneous healing occurred in some cases. Its appearance was a poor prognostic sign because acquired immunodeficiency syndrome developed in a significant proportion of patients within a few months of onset.

Atypical early syphilis in an hiv-infected homosexual male.

A homosexual male, seropositive to HIV and with previously documented syphilitic infections, developed a slowly growing nodule on his left wrist (possibly a chancre) followed, after 2 months, by a few scattered, large papular lesions. Serological evidence of active syphilis was obtained and treponema were identified in the initial lesion by means of immunofluorescent staining. Treatment with both aqueous crystalline penicillin G and benzathine penicillin G healed the lesions. This represents a further case of an atypical presentation of early syphilis in an immunocompromised host.