Evaluating the Clinical Meaning of Dermatology Life Quality Index Scores Between Different Phenotypes of Atopic Dermatitis in Patients Before and After Biologic Therapy With Dupilumab.

Background and Objective: Atopic Dermatitis (AD) is the most prevalent inflammatory skin disorder resulting in an intense impact on patients quality of life. The aim of this study is to evaluate the clinical meaning of the DLQI scores documented between different phenotypes of AD patients under biologic therapy with Dupilumab. Method: We conducted a retrospective analysis of 209 patients with AD treated with Dupilumab for 2 years. These patients were categorized into different clinical phenotypes. Severity of the disease was assessed by using the Eczema Area and Severity Index (EASI), Numerical Scale Rating (NRS) for sleep (NRS sleep), pruritus (NRS pruritus) and Dermatology Life Quality Index (DLQI) at baseline and subsequently at 4,12 and 24 months. Results: Our results show that the higher DLQI scores (mean: 18.6, range:9-30) achieved at T0 are associated with a prurigo nodularis AD pattern, while after 24 months (T3) of therapy with Dupilumab, the worst quality of life index results were reported in Flexural and Head-Neck combined clinical phenotypes. Conclusions: Quality of life is probably what matters most as an overall endpoint in AD. Assessing the clinical meaning of DLQI scores across different AD phenotypes could be a further aid when considering decision making factors in patient management.

Targeting tumor necrosis factor-alpha in the therapy of psoriasis.

Tumor necrosis factor-alpha (TNF-alpha) plays a fundamental role in the initiation and persistence of skin inflammation in psoriasis. The best evidence of the essential activity of this cytokine in the pathogenesis of psoriasis came from the observation that selective TNF-alpha blockers are dramatically effective in the therapy of this disease. The TNF-alpha inhibitors, infliximab and etanercept, have been employed with success in moderate to severe psoriasis and in psoriatic arthritis in randomized controlled trials. Anti-TNF-alpha biologicals induce rapid disease resolution and long-lasting remission, suggesting that they may alter the natural course of the disease. Further studies are warranted to more precisely establish the biological bases of the action of anti-TNF-alpha agents, better define which subgroup of patients can benefit most from this treatment, and the modalities of combination therapy with other antipsoriatic agents. Many other TNF-alpha inhibitors have been developed but none of them has been yet used in the therapy of psoriasis. Major limitations to the use of selective TNF-alpha blockers include the reactivation of latent tuberculosis, the risk of opportunistic infections, the development of specific antibodies, which is associated with a reduced duration of response to treatment, and the high cost.

Treatment of recalcitrant scleromyxedema with thalidomide in 3 patients.

Scleromyxedema is a generalized, papular, and sclerodermoid form of lichen myxedematosus associated with monoclonal gammopathy and systemic changes. Despite anecdotal reports of success with various agents, no satisfactory treatments are currently available. We report 3 adult patients with recalcitrant scleromyxedema associated with paraproteinemia who were treated with thalidomide. All 3 patients had marked improvement of the skin lesions and joint mobility after the first 2 months of therapy, with further amelioration after 4 months, and reduction in paraprotein levels.

Identification of the keratin K9 R162W mutation in patients of Italian origin with epidermolytic palmoplantar keratoderma.

Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant skin disorder characterized by hyperkeratosis of the palms and soles associated with histologic findings of hyperkeratosis and epidermolysis. Ultrastructurally, there is vacuolization of the cytoplasm and abnormal keratin filament network with tonofilament clumping. EPPK is caused by mutations in the keratin 9 gene (KRT9), which is expressed exclusively in suprabasal keratinocytes of palmoplantar epidermis. The mutation R162W is the most frequent keratin 9 alteration reported in patients from different geographical areas. We present three unrelated Italian families affected by EPPK in which we confirmed the presence of the R162W mutation, by RT-PCR analysis followed by sequencing of the KRT9 gene, in all affected members. The finding of the same mutation in all patients, together with the previous reports of the disease, strongly suggest that position 162 of the KRT9 gene represents a mutation "hot-spot", probably due to the peculiarity of the sequence.

Disseminated lupus vulgaris.

Lupus vulgaris is the most common form of cutaneous tuberculosis, and usually presents as a solitary lesion on the face. We report two patients with multiple lesions on different skin areas. The first patient presented a diffuse involvement of the right foot, and reddish-brown plaques on the right leg, the back and the face. Spreading of the lesions followed a prolonged application of topical corticosteroids. The second patient showed a large plaque on the nape and occipital area resulting in scarring alopecia, and plaques on the right inguinal and thigh regions. Ziehl-Neelsen staining was negative in both cases, but diagnosis was supported by histology and polymerase chain reaction analysis. No visceral involvement was present. Antituberculosis polychemotherapy was rapidly effective.

Autoimmune progesterone dermatitis.

Autoimmune progesterone dermatitis (APD) is a rare disorder characterized by recurrent polymorphous skin manifestations, which appear or are exacerbated during the luteal phase of the menstrual cycle. The hallmarks for diagnosis include premenstrual flare, its prevention with the inhibition of ovulation, and positive skin reaction to intradermal injection of progesterone. The mainstay of treatment is to inhibit the secretion of endogenous progesterone by suppressing ovulation. Bilateral oophorectomy may be necessary in patients with severe and refractory symptoms. We report herein the case of a 38-year-old woman who developed recurrent and cyclic vesiculobullous eruptions clinically suggestive of erythema multiforme or autoimmune bullous diseases. The skin manifestations turned out to be APD. The patient was treated with tamoxifen 20 mg daily with complete symptom remission after 4 months.

Subacute cutaneous lupus erythematosus induced by nifedipine.

BACKGROUND: Subacute cutaneous lupus erythematosus (SCLE) has been reported to be associated with the use of several drugs, including thiazides, terbinafine, and, rarely, calcium channel blockers. OBJECTIVE: A case of SCLE induced by nifedipine is presented. METHODS AND RESULTS: A 48-year-old white woman developed a papulosquamous and annular eruption in sun-exposed areas during the summer. The patient was taking nifedipine for essential hypertension for four years. Serology showed the presence of antinuclear and anti-Ro/SSA as well as antihistone antibodies. Histopathologic and immunopathologic (granular IgM deposits at the dermoepidermal junction) findings confirmed the diagnosis of SCLE. Nifedipine discontinuation led to rapid improvement with almost complete resolution of skin lesions in one month in the absence of active treatment. Reduction of antinuclear, anti-Ro/SSA, and antihistone antibody levels was documented after six months. CONCLUSION: Nifedipine can cause SCLE after a long period of administration. Antihistone antibodies may be associated with drug-induced SCLE.

Nodular perianal herpes simplex with prominent plasma cell infiltration.

BACKGROUND: Nodules are exceptional manifestations of herpes simplex virus (HSV) infection in immunocompromised patients. Only two cases of nodular HSV-2 infection of the perianal region have been reported previously. GOAL: The case of a 46-year-old homosexual man with AIDS presenting with painful perianal nodules resembling squamous cell carcinoma is described. STUDY DESIGN: This case report presents details of the histologic findings and treatment regimen. RESULTS: Histologic examination showed the presence of rare multinucleated giant epithelial cells and a dense inflammatory infiltrate composed mostly of plasma cells. Polymerase chain reaction analysis was positive for HSV-2 and negative for HSV-1, cytomegalovirus, Epstein-Barr virus, and human herpesvirus types 6 and 7. After being treated ineffectively with oral acyclovir (4 g/d) for 15 days, the patient was treated with oral valacyclovir (6 g/d), resulting in marked improvement in 10 days and complete resolution after 2 months. CONCLUSIONS: In immunocompromised patients, HSV-2 infection may present with atypical clinical and histopathological features.

Localized cutaneous hyalohyphomycosis caused by a Fusarium species infection in a renal transplant patient.

Fusariosis is a hyalohyphomycosis due to Fusarium species that mainly occurs in immunocompromised hosts. The clinical spectrum of Fusarium infection comprises localized and disseminated forms. A case of localized cutaneous fusariosis caused by Fusarium solani in a renal transplant patient is described, and the skin manifestations of the disease are discussed.

Papular neutrophilic dermatosis and erythema elevatum diutinum following erythropoietin therapy in a patient with myelodysplastic syndrome.

A 65-year-old man with refractory anaemia with an excess of blasts developed an erythematous papular eruption symmetrically distributed on the legs and trunk 3 months after initiation of erythropoietin therapy. The lesions showed a dense neutrophilic infiltrate in the absence of leucocytoclastic vasculitis, and did not fit the criteria of a well-defined neutrophilic dermatosis. Concomitant with the rapid resolution of these skin lesions following erythropoietin discontinuation, typical lesions of erythema elevatum diutinum arose on the extensor surface of the fingers, knees and elbows, which responded to a brief course of dapsone treatment. Although typical and atypical neutrophilic dermatoses have been reported in patients with haematological disorders, they have also been associated with the use of drugs, in particular granulocyte colony-stimulating factor. To our knowledge this is the first report of unclassified neutrophilic dermatosis and erythema elevatum diutinum occurring following the administration of erythropoietin.