The role of inflammatory markers in assessing disease severity and response to treatment in patients with psoriasis treated with etanercept.

BACKGROUND: Psoriasis is a chronic, systemic, inflammatory disease. Inflammatory markers are used in clinical practice to detect acute inflammation, and as markers of treatment response. Etanercept blocks tumour necrosis factor (TNF)-α, which plays a central role in the psoriatic inflammation process. AIM: To reveal any possible association between disease severity [measured by Psoriasis Area and Severity Index (PASI)] and the inflammatory burden (measured by a group of inflammatory markers), before and after etanercept treatment. METHODS: In total, 41 patients with psoriasis vulgaris, eligible for biological treatment with etanercept, were enrolled in the study. A set of inflammatory markers was measured, including levels of white blood cells and neutrophils, fibrinogen, ferritin, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), haptoglobin, ceruloplasmin and α1-antitrypsin, before and after 12 weeks of etanercept 50 mg twice weekly. RESULTS: All markers were reduced after treatment (P < 0.001). PASI correlated with fibrinogen and hs-CRP. Of the 41 patients, 19 (46.3%) achieved reduction of 75% in PASI (PASI75). An increase in hs-CRP and ESR difference (values before minus values after treatment) was related to higher likelihood of achieving PASI75. CONCLUSIONS: Inflammatory markers, particularly hs-CRP and to a lesser extent, fibrinogen and ESR, can be used to assist in assessing disease severity and response to treatment in patients with psoriasis. A combination of selected inflammatory factors (which we term the Index of Psoriasis Inflammation) in combination with PASI might reflect inflammatory status in psoriasis more accurately than each one separately.

Development of two primary malignant melanomas after treatment with adalimumab: a case report and review of the possible link between biological therapy with TNF-alpha antagonists and melanocytic proliferation.

Biologics, such as tumor necrosis factor alpha (TNF-alpha) antagonists, have revolutionized treatment of several significant inflammatory autoimmune diseases. Nevertheless, issues concerning long-term safety remain to be clarified. There is growing evidence linking biological treatments with the occurrence of malignancies or reactivation of latent ones, including malignant melanoma. We report the case of a 75-year-old male patient who developed 2 primary malignant melanomas (MM) after treatment with adalimumab for rheumatoid arthritis. He was under adalimumab treatment for approximately 12 months before the diagnosis of MM on his right lower leg. After surgical removal and staging, no evidence of metastases was found. A few months later, a second MM developed on the patient's scalp. The short duration of treatment with adalimumab and the unclear temporal relationship cannot adequately support a probable link between this double MM occurrence and the adalimumab-induced immunosuppressive state. The result of a literature search regarding the possible association between anti-TNF drugs and melanocytic proliferation is provided.

Erythema multiforme following vaccination for human papillomavirus.

Erythema multiforme (EM) is an acute self-limited immune-mediated reaction manifested by target skin lesions with mucous membrane involvement. The most common causes are infections and drugs. Vaccinations have been reported as a triggering factor, and they may be a frequent cause of EM in childhood. A 19-year-old female developed several target lesions of the hands and feet 10 days after the second dose of human papillomavirus (HPV) vaccine. Clinico-histologically, a diagnosis of EM minor was made. Treatment with topical corticosteroids and oral antihistamines resulted in complete clearance of the rash. Four months later, she received the last booster dose of the vaccine. A few subtle lesions appeared and disappeared spontaneously after a few days. Gardasil is a non-infectious vaccine, developed for the prevention of cervical cancer, precancerous genital lesions and genital warts. It delivers the major capsid (L1) protein of HPV types 6, 11, 16 and 18. Mild local reactions are the main adverse events. The only serious events are very rare cases of anaphylaxis. In our patient, the temporal relationship between the development of EM and the vaccination suggests that the HPV vaccine probably was the causal agent. This is the first published case of EM following HPV vaccination.

A randomized, double-blind, vehicle-controlled study of a preparation containing undecylenoyl phenylalanine 2% in the treatment of solar lentigines.

BACKGROUND: Solar lentigines are common, benign, cosmetically disfiguring lesions. Available physical treatments are effective, but they are costly and carry risks of side-effects. OBJECTIVE: To evaluate the efficacy and safety of a preparation containing undecylenoyl phenylalanine 2% in the topical treatment of solar lentigines. METHODS: In total, 36 patients with solar lentigines of the hands were randomly assigned to apply the active preparation on one side and the vehicle alone on the other side, twice daily for 12 weeks. Patients were evaluated monthly for efficacy and safety. RESULTS: In all, 30 patients (28 women and 2 men; age range 47-75 years) completed the study. The duration of lesions ranged from 8 months to > 10 years. All patients responded partially on the side of the active treatment. Of the partial responders, 19 (63.3%) had moderate improvement and 11 (36.6%) had marked improvement. Improvement was evident from the first follow-up visit. On the side of the vehicle, 26 remained stable (86.6%) and 4 (13.3%) had partial improvement. There was a significant difference (P < 0.01) in efficacy of the active preparation vs. the vehicle. Using patient assessment ratings, 80% were 'much more satisfied/more satisfied' with the result. The reported side-effects were minor and included erythema and itching or burning on the side of active treatment. CONCLUSIONS: Undecylenoyl phenylalanine 2% is a novel depigmenting agent, which possibly acts as an alpha-melanocyte-stimulating hormone antagonist, thus inhibiting melaninogenesis. It achieved a significant lightening of the lesions with minimal side-effects. Most patients were satisfied with the improvement. Undecylenoyl phenylalanine 2% may represent a safe, effective and inexpensive therapeutic alternative for solar lentigines.

An epidemiological study of syphilis incognito, an emerging public health problem in Greece.

BACKGROUND: Syphilis incognito is a subtype of latent syphilis (early or late) characterized by no signs or symptoms of primary or secondary syphilis and diagnosed by positive serologic results for syphilis during routine screening. OBJECTIVE: To study the epidemiological characteristics, causes, and implications of syphilis incognito in Greece. PATIENTS AND METHODS: All new adult patients diagnosed as having syphilis in Andreas Sygros Hospital for Skin and Venereal Diseases, Athens, Greece, from 1989 through 1996 were studied prospectively and retrospectively (history, physical examination, serologic tests, cerebrospinal fluid examination, and imaging) to determine the stage of their disease. The epidemiological, clinical, and serologic characteristics of patients with syphilis incognito were recorded and analyzed. RESULTS: During the 8-year period, 711 new syphilis cases were detected; of these, 480 cases (67.5%) fulfilled the definition criteria of syphilis incognito. The male-female ratio was 1.8:1. Patients with syphilis incognito were most commonly heterosexual, had a median socioeconomic status, and were aged 20 to 39 years, and their conditions were diagnosed during routine screening for syphilis (prenatal care, hospital admission, or blood donation). However, the number of syphilis incognito cases appeared to decline during the period studied. CONCLUSIONS: The incidence of syphilis in Greece has decreased dramatically, following the trends in western Europe. The most common form of syphilis is syphilis incognito, affecting adults who are older and have a higher socioeconomic status than those in the past. Improved hygiene and wide use of antibiotics that minimize or abolish symptoms of early disease may have contributed to the frequency of syphilis incognito in recent years. Screening of asymptomatic persons, especially those at high risk, should continue and be reenforced to prevent the devastating consequences of unrecognized and untreated syphilis.

Lack of reactivation of cytomegalovirus retinitis in an AIDS patient, during and after stopping long-term cidofovir treatment: case report.

The case of an AIDS patient with cytomegalovirus (CMV) retinitis who was treated with cidofovir for 17 consecutive months, without any adverse effect, is presented. In the context of antiretroviral therapy, cidofovir therapeutic regimen was 5 mg/kg of body weight for 2 weeks and 5 mg/kg thereafter every other week. Probenecid, hydration and monitoring for proteinuria were also used to prevent nephrotoxicity. The patient stopped maintenance therapy for CMV retinitis after the permanent rise of CD4+ cells above 100 c/mm3. For more than 10 months after drug withdrawal the patient remains free of retinitis.

Experience with adriamycin, bleomycin, vincristine (ABV) palliative chemotherapy in advanced AIDS-related Kaposi's sarcoma.

After administration of Adriamycin, bleomycin, vincristine (ABV) as palliative chemotherapy in advanced AIDS-related Kaposi's sarcoma (AIDS.KS) patients with low Karnosfsky performance scores, the authors attempted to estimate the overall biological cost/benefit relating to the disease. The authors analyzed data from 20 consecutive AIDS patients with advanced Kaposi's sarcoma presenting skin and visceral involvement treated with ABV every 3 weeks. An increased rate of infections, HIV and ABV-related side effects was observed. The performance amelioration (about 30%) was not significantly correlated with AIDS.KS clinical remission. CD4 count at baseline (p < 0.05), ABV therapy duration (p < 0.001), the achieved AIDS.KS clinical amelioration score (p < 0.01) and the improved Karnofsky score (p < 0.001) were significant predictors of life expectancy which was unrelated to the rate of side effects. The authors conclude that ABV palliative chemotherapy can assist in protracting life expectancy and improving the Karnofsky score.

An overview of classic Kaposi's sarcoma in Greece.

Classic Kaposi's sarcoma (CKS) is a rare tumor affecting mainly the elderly and running a chronic and indolent course. CKS in Greece is not uncommon with an estimated annual incidence of 0.47/1000,000 population, representing 1.35% of all malignant neoplasms. Furthermore, it is characterised by endemic clustering and clinico-epidemiological peculiaritis, supporting the speculation that it may represent a distinct form, the Mediterranean Kaposi's sarcoma, or a subtype of CKS. Kaposi's sarcoma is a multicentric angiomatous tumor of obscure etiopathogenesis and histogenesis. Based on clinical and epidemiological grounds, four distinct forms have been recognized: classic or sporadic, African or endemic, iatrogenic and epidemics or AIDS-associated KS [1].

Long-term follow-up of endoscopic therapy of anal canal condylomata acuminata with podophyllotoxin.

BACKGROUND: Condylomata acuminata of the anal canal, a common sexually transmitted disease, are difficult-to-treat lesions with a high recurrence rate after initial successful treatment. OBJECTIVE: Our aim was to evaluate by anoscopy the efficacy of podophyllotoxin 0.5% solution topically applied for the treatment of anal warts. METHODS: We prospectively studied consecutive patients with condylomata acuminata of the anal canal that spared the rectum. They were treated with 0.5% podophyllotoxin solution topically applied on the warts, by anoscopy. Podophyllotoxin solution was administered on days 1, 2 and 3 every week (a treatment cycle) for a maximum of 4 weeks. Patients whose warts were not completely eradicated were classified as failures. Follow-up anoscopy was performed monthly for the first 6 months and every 6 months thereafter. Those who relapsed during the follow-up period were retreated. RESULTS: Twenty-two immunocompetent patients entered the study. The primary clearance rate was 22.7, 54.5, 68.1 and 86.3% after 1, 2, 3 and 4 treatment cycles, respectively. During the follow-up period (46, 12-60 months), seven patients (36.8%) relapsed. Four of them were successfully retreated. Thus, a complete cure was achieved in 16 out of 22 patients (72.7%). Adverse side-effects were mild. They included proctalgia in six (27.2%), bleeding in four (17.2%), and both proctalgia and bleeding in two (9%) patients. CONCLUSIONS: Endoscopic topical application of 0.5% podophyllotoxin solution is an effective and well-tolerated method for the treatment of condylomata acuminata of the anal canal.

Poikiloderma of Civatte: a histopathological and ultrastructural study.

BACKGROUND: Poikiloderma of the face and neck (Civatte) has not been studied in depth for decades, especially as far as the histopathology is concerned. MATERIAL AND METHODS: We studied 50 consecutive patients with poikiloderma of Civatte (PC). Their evaluation included: history, physical examination, lesional skin biopsy and histological examination of sections stained with hematoxylin-eosin, PAS, Fontana-Masson, acid orcein Giemsa for elastic fibers and toluidine blue for mast cells. In 10 randomly selected subjects, a second skin biopsy was performed and specimens were examined under the electron microscope. RESULTS: There were 34 females (68%) and 16 males. The mean age at diagnosis was 47.8 years for females and 61.7 years for males. Histological examination revealed an atrophic (62%), flattened (84%) epidermis with hyperkeratosis (92%) and occasional follicular plugging (34%). In some cases, mild hydropic degeneration of the basal cell layer was evident (46%). Melanin was irregularly distributed in the lower epidermis (94%), and melanophages were often present in the dermis (92%). The most prominent and constant feature (100%) was solar elastosis of the papillary dermis. The blood vessels were almost invariably dilated (96%) with a mild perivascular lymphohistiocytic infiltrate (78%), sometimes with plasmacytes (56%). At the ultrastructural level, the epidermis showed only minor changes. The dermoepidermal junction was intact. The most constant findings were swelling and disruption of the collagen fibers as well as focal degeneration of the collagen bundles. Occasionally, several vacuolar spaces were found just under the basal lamina. Melanin-laden macrophages scattered in the dermis were also detected. CONCLUSIONS: PC shows distinct histological and ultrastructural features, supporting the theory that it represents a separate entity. The histology of PC is characteristic but not pathognomonic. On this basis, the differential diagnosis from Riehl's melanosis, poikiloderma atrophicans et vasculare and other acquired poikilodermas can be made. Ultrastructural findings were consistent with the histological findings. Changes of the dermal connective tissue (solar elastosis) predominated, providing morphological evidence for the role of ultraviolet radiation in the pathogenesis of PC.

Altered innate and adaptive immune responses in patients with hidradenitis suppurativa.

BACKGROUND: The clinical improvement of hidradenitis suppurativa reported in a small number of patients with antitumour necrosis factor (anti-TNF)-alpha therapies supports the hypothesis for an altered immune response in these patients. OBJECTIVES: To evaluate the state of the innate and adaptive immune responses in patients with hidradenitis suppurativa. METHODS: Fifty-three patients and six healthy controls were studied. Blood was sampled and subpopulations of lymphocytes were analysed by flow cytometry; monocytes were isolated and their function was evaluated from the concentrations of TNF-alpha and interleukin (IL)-6 in supernatants of cell cultures after triggering with endotoxins (lipopolysaccharides). TNF-alpha and IL-6 were estimated by an enzyme immunoassay. RESULTS: CD3/CD8 lymphocytes were lower in patients with involvement of the perineum than in controls; patients with involvement of the breast had higher levels of natural killer (NK) cells than controls. A negative correlation was found between years lapsing since initial presentation of lesions of hidradenitis and the percentage of NK cells. Monocytes isolated from healthy volunteers were more active for the secretion of TNF-alpha and IL-6 than those of patients with hidradenitis suppurativa. CONCLUSIONS: A reduction in the percentage of NK cells over time and a lower monocyte response to triggering by bacterial components is observed in patients with hidradenitis suppurativa. Further research is needed to clarify if these changes are connected to an autoimmune mechanism in the pathogenesis of hidradenitis suppurativa.

Poikiloderma of Civatte: a clinical and epidemiological study.

BACKGROUND: Although a common dermatosis, idiopathic poikiloderma of the face and neck has not been studied in depth for decades. OBJECTIVES: To reassess the clinical and epidemiological characteristics of poikiloderma of Civatte (PC). MATERIAL AND METHODS: Fifty consecutive patients with PC. Evaluation included history taking and physical examination. Epidemiological and clinical parameters were recorded and analysed. The literature from 1923 until today, was reviewed thoroughly. RESULTS: The frequency of PC among dermatologic patients was estimated to be 1.4%. There were 34 females (68%) and 16 males in the present study. The mean age at diagnosis was 47.8 years for females and 61.7 years for males. The majority (88%) had skin phototype II or III. Among females, 26 were at their peri-menopausal stage, including three cases of iatrogenic menopause. Four patients reported that other blood-related family members also had PC. The v and the sides of the neck and the upper chest were most often affected in a symmetric distribution. The face (preauricular and parotid region) was involved in 19 patients (38%). The erythemato-telangiectatic clinical type predominated (58%), followed by the mixed (22%) and the pigmented type (20%). Almost half of the patients (46%) were symptomatic (itching, burning and 'flushing'). The mean duration from onset to diagnosis was 6.2 years according to the patients' report. The course was usually slowly progressive (82%) and irreversible. CONCLUSIONS: PC shows characteristic features, supporting the theory that it represents a distinct entity. It is rather common in Greece. Although menopausal women predominated in our cohort, men were not uncommonly affected and were diagnosed at an older age. Based on the predominating clinical feature, PC can be classified into three clinical forms. Symmetry and sparing of the anatomically shaded areas of the neck are highly characteristic for PC. Face involvement was not as common and as severe as it had been considered in the past. Recognition of clinical type is important for the selection of the most appropriate treatment, which, despite the advent of novel modalities, remains problematic.

Papulonodular lichenoid and pseudolymphomatous reaction at the injection site of hepatitis B virus vaccination.

Immunization with the hepatitis B virus (HBV) is effective and safe with an estimated incidence of adverse reactions, either local or systemic, of less than 0.1%. Cutaneous side effects are rare and include lichen planus (LP) and lichenoid reactions. We report the case of a 21-year-old female, in whom a persistent, papulonodular lesion developed at the site of the injection, 6 weeks after the second dose of the HBV. Histological examination revealed lichenoid and pseudolymphomatous features. In addition, sensitization to thiomersal, a vaccine constituent, was documented by patch testing. The association of LP with chronic liver disease is well established. Furthermore, less than 20 cases of lichen or lichenoid reactions, following HBV vaccination, have been reported. Although several arguments have been presented, it is still debated whether there is a causal association or the occurrence of LP following HBV vaccination is a simple coincidence. It has been speculated that a T-cell-mediated, graft-versus-host-like reaction, triggered by a sensitizing protein, is directed against keratinocytes expressing an epitope of hepatitis B surface antigen or a similar epitope. Our case may represent a localized lichenoid reaction to HBV vaccination, a local reactive hyperplasia or a persisting delayed hypersensitivity reaction to a vaccine constituent. This is the first case of a local lichenoid reaction at the injection site of the HBV vaccine, providing further documentation for a causal association linking the HBV vaccine with LP.

Pretibial myxedema as the initial manifestation of Graves' disease.

Pretibial myxedema (PM) is a localized thickening of the pretibial skin due to accumulation of acid mucopolysacharides (glycosaminoglycans). Its pathogenesis is still under investigation. Pretibial myxedema, exophthalmus and thyroid acropachy are the dassic extrathyroidal manifestations of Graves' disease. Almost invariably, PM follows the onset of ophthalmopathy, developing after the diagnosis and treatment of hyperthyroidism. Pretibial myxedema preceding Graves' ophthalmopathy is rare. We report the case of a 28-year-old Greek woman, who presented with multiple, asymptomatic nodules and plaques of the lower legs in the absence of other physical findings. Histopathologic examination revealed deposition of mucopolysacharides in the lower dermis. Laboratory investigation showed elevated serum T3 and T4 and depressed TSH levels. In our patient, pretibial myxedema was the earliest manifestation, leading to the diagnosis of Graves' disease.