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.

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.

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.

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.

Oral inosiplex in the treatment of cervical condylomata acuminata: a randomised placebo-controlled trial.

Conventional therapies for human papillomavirus infection aim to remove clinically apparent lesions, while latent infection may remain, representing a threat for transmission and carcinogenesis. The use of a systemic agent may more effectively control the virus. We conducted a randomised placebo-controlled study to investigate the efficacy and safety of oral inociplex in the treatment of cervical condylomata acuminata (CA) that had been resistant to conventional therapies. Thirty-eight white European women, aged 20-43 years, with genital warts of the cervix, refractory to at least one conventional therapy, were randomly assigned to receive either inosiplex, 50 mg/kg daily peros for 12 weeks (group 1), or placebo (group 2). Of the 17 evaluable group 1 women, 4 responded to the treatment completely, 7 responded partially and 6 did not respond. Of the 19 group 2 women, none responded to the treatment completely, 3 responded partially and 16 did not respond. The therapeutic difference between women receiving active and placebo therapy was statistically significant (chi(2)= 6.69, P < 0.01) and remained significant when an intention-to-treat analysis was performed (chi(2)= 7.69, P < 0.01). None of the complete responders experienced recurrence during the 12-month follow up. Adverse effects were mild and resolved upon completion of therapy. Compared with placebo, inosiplex showed considerable efficacy with insignificant and reversible adverse effects and without recurrences. Inosiplex may represent an efficacious and safe alternative systemic form of therapy for cervical genital warts.