European expert consensus statement on the systemic treatment of alopecia areata.

Alopecia areata is an autoimmune form of non-scarring hair loss. It is usually characterized by limited areas of hair loss. However, the disease may progress to complete scalp and body hair loss (alopecia totalis, alopecia universalis). In patients with alopecia areata hair loss significantly impacts the quality of life. Children and adolescents with alopecia areata often experience bullying, including physical aggression. The disease severity evaluation tools used in clinical practice are: the Severity of Alopecia Tool (SALT) score and the Alopecia Areata Scale (AAS). A SALT score equal to or greater than 20 constitutes a commonly accepted indication for systemic therapy in alopecia areata. When using the AAS, moderate to severe alopecia areata should be considered a medical indication for systemic treatment. Currently, the only two EMA-approved medications for alopecia areata are baricitinib (JAK 1/2 inhibitor) for adults and ritlecitinib (JAK 3/TEC inhibitor) for individuals aged 12 and older. Both are EMA-approved for patients with severe alopecia areata. Other systemic medications used off-label in alopecia areata include glucocorticosteroids, cyclosporine, methotrexate and azathioprine. Oral minoxidil is considered an adjuvant therapy with limited data confirming its possible efficacy. This consensus statement is to outline a systemic treatment algorithm for alopecia areata, indications for systemic treatment, available therapeutic options, their efficacy and safety, as well as the duration of the therapy.

Improvement in Hidradenitis Suppurativa and quality of life in patients treated with adalimumab: Real-world results from the HARMONY Study.

BACKGROUND: Hidradenitis suppurativa (HS), a chronic, recurrent, debilitating skin disease, is characterized by painful, inflammatory, subcutaneous lesions of the axilla, inguinal and anogenital regions. Overall prevalence of HS is ˜1%, and the impact of disease on patient quality of life (QoL) and healthcare resource utilization (HRU) is high. OBJECTIVES: To estimate the real-world effectiveness of adalimumab (Humira®) treatment in patients with moderate-to-severe HS on disease severity, pain, QoL, work productivity and HRU. METHODS: HARMONY (Effectiveness of Adalimumab in Moderate to Severe HidrAdenitis SuppuRativa Patients - a Multi-cOuNtry studY in Real Life Setting) is a multicentre, postmarketing observational study in adult patients with moderate-to-severe HS. Disease severity and QoL parameters were evaluated using validated measures at 12-week intervals over 52 weeks of treatment. The primary endpoint was the proportion of patients achieving a Hidradenitis Suppurativa Clinical Response (HiSCR: ≥50% reduction in abscess and inflammatory nodule count, with no increase in abscess and draining fistula counts relative to baseline) at 12 weeks. Secondary endpoints were HiSCR at 24, 36 and 52 weeks and changes in QoL parameters and work productivity assessments. Analyses were conducted using as-observed data. RESULTS: The proportion of patients reaching the primary HiSCR endpoint was 70.2% (n = 132/188 enrolled) and remained ≥70% until study completion. There were statistically significant (P < 0.0001) reductions in worst and average skin pain. All of the QoL measures evaluated improved significantly (P < 0.0001) by 12 weeks of adalimumab treatment, as did work productivity assessments (P < 0.05), and there was a ˜50% decrease in HRU between baseline and week 52. Adalimumab was well tolerated. CONCLUSIONS: In this real-world setting, adalimumab treatment of moderate-to-severe HS resulted in decreased disease severity and improvements in QoL and productivity. Response to adalimumab was rapid (within 12 weeks) and sustained (52 weeks). No unexpected safety signals were reported.

Letter: Human papilloma virus and molluscum contagiosum lesions related to infliximab therapy for psoriasis: a case series.

INTRODUCTION: Biological therapy for psoriasis exerts its action via an immunomodulatory and eventually immunosuppressive mode. Immunosuppression is linked to HPV flares. Our purpose is to investigate a possible relationship between infliximab therapy for psoriasis and human papilloma virus and molluscum (HPV/MC) infections. METHODS: We report a case series of three patients with psoriasis on infliximab, who developed HPV/MC lesions following their treatment. RESULTS: Our patients developed HPV/MC lesions within a few months after the initiation of infliximab infusions for psoriasis. DISCUSSION: Immunosuppresion is related to HPV/MC flares. Biological therapy and in particular infliximab treatment acts by immunomodulation and eventually a degree of immunosuppression. CONCLUSIONS: Anti-TNF treatment could be associated with HPV and/or MC flares. For this reason, we suggest the consideration of obtaining a routine cervical PAP smear before the commencement and during treatment with anti-TNF agents for psoriasis.

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.

Topical retinoids in the treatment of aging of the skin.

Aging of the skin is a complex phenomenon resulting from the interaction of several intrinsic and extrinsic factors [1]. Due to the cosmetic disfigurement it produces and its psychological impact, especially to women, aging of the skin has become an issue of great social significance and concern. Intrinsic aging is an inevitable, genetically programmed process, the underlying mechanisms of which remain largely unknown. No prevention or effective treatment is currently available [1]. Among extrinsic influences (wind, heat, cigarette smoke, chemicals, etc.), ultraviolet radiation appears to be the single most important factor associated with aging of the skin [2]. Photoaging refers to gross and microscopic cutaneous changes induced by cumulative exposure to ultraviolet radiation (UVR). These changes are superimposed on the background of intrinsic aging [2]. Increased recreational sun exposure, including excessive sunbathing, the depletion of stratospheric ozone, the use of UVR in the treatment of various skin diseases, are some of the causes that have led to increased prevalence of photoaging during the last decades. The clinical importance of photoaging lies mostly on the potential for the development of precancerous lesions or skin cancer [3]. In contrast to intrinsic aging, photodamage can be prevented by sun avoidance and proper sun protection [2]. Furthermore, overwhelming clinical and histological evidence indicate that skin changes of photoaging can be reversed by the use of topical retinoids [4].

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].

Pseudoporphyria associated with nonhemodialyzed renal insufficiency, successfully treated with oral N-acetylcysteine.

Pseudoporphyria (PP) is a relatively rare, photodistributed bullous dermatosis that resembles porphyria cutanea tarda (PCT), but it is not accompanied by porphyrin abnormalities in the serum, urine, or stool. It was initially described in renal failure patients on dialysis. Thereafter, it has been associated with several aetiological factors. We report a case of PP in a 67-year-old woman with mild renal failure, successfully treated with N-acetylcysteine. This is the second reported case of PP developing in nondialyzed chronic renal failure. Such cases support the view that renal impairment itself may play a more important aetiological role in developing PP than it was originally considered.