Intermittent Soft-Tissue Tumor Enlargement in Episodic Angioedema With Eosinophilia Syndrome.

ABSTRACT: Episodic hypereosinophilia and angioedema syndrome, also known as Gleich syndrome, is a rare entity characterized by recurrent episodes of eosinophilia, angioedema, urticaria, fever and weight gain with spontaneous resolution. It is classified as an idiopathic hypereosinophilic syndrome. Unlike other hypereosinophilic syndromes, it has a low risk for internal organ damage. We report the case of a 42-year-old male with a 28-year history of recurrent erythematous wheals and plaques and persistent hypereosinophilia. Physical examination revealed a well-defined subcutaneous nodule on his right lower limb that increased in size with each episode of angioedema. Histopathology evidenced a lipoma with intense eosinophil infiltration within the mature adipose tissue, while the specimen of the wheal revealed scarce perivascular and interstitial eosinophilic inflammatory infiltrate. Diagnosis of episodic angioedema with eosinophilia syndrome was made based on clinical and laboratory findings.

Netherton Syndrome: Case Report and Review of the Literature.

Netherton syndrome (NS) is a rare genodermatosis with an autosomal recessive pattern of inheritance caused by pathogenic variants in the SPINK5 gene. It is characterized by a triad consisting of atopic diathesis, ichthyosis linearis circumflexa, and hair shaft abnormalities. Ichthyosis linearis circumflexa can be confused with atopic dermatitis leading to a delayed diagnosis. Furthermore, difficulty in making the differential diagnosis with other atopiform, erythrodermic, and ichthyosiform entities that exhibit hair shaft abnormalities represent a challenge. Trichoscopy is an accessible and noninvasive auxiliary diagnostic tool in these cases; the hair shaft abnormalities found in NS are bamboo, golf tee, and matchstick hairs. Identification of a pathogenic variant in the SPINK5 gene through genetic testing is necessary to confirm the diagnosis. Multiple treatment options are available including topical therapy with emollients, corticosteroids, calcineurin inhibitors, antiseptics, and narrowband UVB phototherapy. Systemic treatments comprehend intravenous immunoglobulins, and advances in the understanding of the pathophysiology of NS have led to more directed therapies with biologics such as infliximab, ixekizumab, secukinumab, ustekinumab, and dupilumab. Treatments currently under investigation include inhibitors of kallikrein 5, cathelicidins, drugs activating the transcription factor nuclear factor erythroid-derived 2-like 2, and gene therapy using autologous keratinocytes induced with a lentiviral vector encoding SPINK5.

Indurated Plaques on the Legs: Think Lymphoma.

Dear Editor, Primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT) is a rare and aggressive neoplasm. A timely diagnosis may prevent fatal outcomes; physicians should take this entity into consideration when assessing non-specific lesions on the lower limbs. We present a 69-year-old woman with a 1-month history of a firm plaque on her left leg. Physical examination revealed an asymptomatic, indurated, smooth, and erythematous plaque on the pretibial region of her left extremity (Figure 1, a). The rest of the physical examination was normal. Histological examination revealed cohesive sheets of a dense cell infiltrate in the dermis, composed of large round immunoblast-type cells with prominent nucleoli, and the presence of mitoses. Immunohistochemical stains were positive for CD20, Bcl2, and MUM1 (Figure 1, b-d). Additionally, c-MYC and Ki67 exhibited a 20% positivity; CD3 and CD10 were negative. The diagnosis of PCDLBCL-LT was established. Imaging and blood workup ruled out systemic involvement. Treatment with R-CHOP chemotherapy was initiated, with complete tumor regression by the third cycle. The patient completed 6 cycles and has remained disease-free after 18 months. Primary cutaneous B-cell lymphomas (CBCL) are lymphoproliferative disorders that appear on the skin without evidence of extracutaneous manifestations at the time of diagnosis (1). They represent 25 to 35% of all primary cutaneous lymphomas (2). In 2018, an updated version of the 2008 WHO-EORTC classification divided CBCLs into 5 subtypes: PCDLBCL-LT, primary cutaneous marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU), and intravascular large B-cell lymphoma (3). PCDLBCL-LT is the least common subtype, representing approximately 10% of all CBCLs and only 4% of all cutaneous lymphomas (2,3). Although the pathogenesis for most CBCLs is still unknown, positive serology for Lyme disease in a significant number of patients has been recognized as a probable etiologic association (4). PCDLBCL-LT is more frequent in women, and the mean age of presentation is 76 years. It usually presents as erythematous or bluish nodules, and up to 75% of the cases appears on one or both legs (1). Although infrequent, other locations have been reported, including the head, neck, trunk, and upper extremities (5). Workup should include a complete physical exam, skin biopsy, blood tests, and imaging (2,3). Histopathology shows a diffuse infiltrate in the dermis composed of large B-cells (centroblasts and/or immunoblasts) with extension to subcutaneous cellular tissue. These cells have round nuclei that are more than twice the size of normal lymphocytes, with prominent nucleoli. The immunophenotype of PCDLBCL-LT is CD20+, CD79a+, CD10-, and Bcl-6+/-, and strongly expresses Bcl-2, MUM1/IRF4, and FOX-P1 (1-3). Unlike the other indolent subtypes, PCDLBCL-LT is generally more aggressive with a poor prognosis. The 5-year disease survival rate is of approximately 50% (5). Management depends on the body surface area, location, and the patient's age and general health. To date, chemotherapy with R-CHOP remains the first line of therapy for PCDLBCL-LT, resulting in complete remission in up to 92% of cases (2). The prognostic characteristics of most PCDLBCL-LTs require timely and appropriate diagnosis and treatment.

Cutaneous manifestations of Castleman disease.

BACKGROUND: Castleman disease (CD) is a lymphoproliferative B-cell disease that is diagnosed from lymphoid hyperplasia with vascular proliferation. Symptoms may include fever, night sweats, and weight loss. Cutaneous manifestations often may go unnoticed since little has been described in the literature regarding them. MATERIALS AND METHODS: A search of CD with cutaneous manifestations was performed in PUBMED, ProQuest, Ovid, Scopus, EMBASE, and Medline. All articles included patients over 18 years of age with a diagnosis of CD and cutaneous manifestations. RESULTS: A total of 68 articles were included. The most common cutaneous manifestations include paraneoplastic pemphigus and erythematous-brown plaques, papules, or nodules. Patients presenting with these manifestations should always have a thorough physical exam, and clinicians should try to identify any palpable lymph nodes. A complete workup to rule out other neoplasias needs to be performed as well. CONCLUSIONS: A better understanding of these skin manifestations of CD may help physicians promptly diagnose and reconsider the path of diagnostic tests to identify this entity.

Local secretion of stress hormones increases in alopecia areata lesions after treatment with UVA-1 phototherapy.

Alopecia areata (AA) is an autoimmune disease of the hair follicle. Keratinocytes of the hair follicle generate an immunosuppressive environment by the local secretion of hormones of the hypothalamic-pituitary-adrenal axis of the skin (skin HPA analog). Our objective was to measure the local production of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and α-melanocyte-stimulating hormone (α-MSH) in the scalp tissue of patients with AA before and after ultraviolet A1 (UVA-1) phototherapy to determine their role in the pathogenesis of AA and the effect of UVA-1 on the AA hormonal environment. This was a retrospective and descriptive study of skin samples from 22 patients with AA before and after UVA-1 treatment. We compared the changes in the local hormonal environment by measuring CRH, ACTH, type 2 melanocortin receptor (ACTH receptor) and α-MSH with immunohistochemical stains. The positivity of MSH was significantly higher (P = .037) in the post-treatment samples compared with the baseline value. ACTH was significantly higher in intensity (P = .032) in the post-treatment samples compared with the initial value. CRH was significantly higher in intensity (P = .013) in baseline samples compared with the final biopsies. The positivity of the ACTH receptor MC2R was not different between the two groups (P = .626). In AA, an interruption in the signalling of CRH could decrease the local concentration of ACTH and MSH, and consequently, the immunosuppressive effect of these hormones. This phenomenon is normalized in the skin treated with UVA-1. A defective signalling system in the cutaneous HPA axis may be involved in the pathogenesis of AA.

A Case of Bullous Morphea Resistant to Methotrexate and Phototherapy Successfully Treated With Mycophenolate Mofetil.

Bullous morphea is rare clinical variant of localized scleroderma characterized by the formation of bullae on sclerotic morphea plaques. Severe disease may be highly disabling and greatly impair quality of life. Current treatment strategies are based on anecdotal reports of clinical experience and include topical corticosteroids, methotrexate and phototherapy. Herein, we describe the case of a 56-year-old woman with progressive bullous sclerotic lesions who was successfully treated with mycophenolate mofetil after treatment failure with psoralen plus ultraviolet A therapy, ultraviolet A1 phototherapy, and methotrexate. Treatment with mycophenolate mofetil halted disease progression after 8 weeks. No major adverse effects were recorded in a 3-year follow-up with continuous treatment. This case suggests mycophenolate mofetil may be considered as an alternative for the treatment of resistant bullous morphea lesions. J Drugs Dermatol. 2018;17(10):1123-1125.

Escalating dosimetry of UVA-1 in the treatment of alopecia areata.

BACKGROUND: Phototherapy can be an option in unresponsive alopecia areata (AA); however, variable results have been reported with its use. We could not find literature of treatment with UVA-1 in AA. A study was designed to evaluate progressive dosimetry to determine the initial dose and its increments. METHODS: Patients with unresponsive AA were recruited. Twenty-five sessions of 30 J/cm2 were administered. If hair regrowth was <75%, the dose was escalated to 60 J/cm2 . If hair improvement remained <75%, an additional 25 sessions at 120 J/cm2 were indicated. If total hair regrowth occurred before 75 sessions, a final visit was performed for biopsies and severity of alopecia tool (SALT) evaluation. Clinical and histopathological assessments were performed blindly. Adverse effects were recorded. RESULTS: Nine men and 13 women were included; 16 were initially S1 , one S3 , and five S4 . Median age was 32 years and median evolution 10 months. Nine patients achieved an S0 , eight S1 , and five S4 (P = 0.005). The most notable improvement was with 60 J/cm2 (P = 0.02). Biopsies exhibited an absence of inflammation in five patients and mild persistence in 17. An increase of 43.75% in anagen hairs (P ≤ 0.001) was achieved, telogen hairs decreased 16.3% (P = 0.06), and catagen hairs were reduced 22.7% (P = 0.005). Pearson's correlation was -0.82 and P ≤ 0.001, when correlating anagen hairs with final SALT. Improvement has continued for 6 months post treatment. Mild xerosis was observed in all patients, and six (28.6%) developed transient mild hyperpigmentation. CONCLUSIONS: This study provides a basis for UVA-1 dosimetry evaluating its therapeutic value in AA.

The efficacy and safety of tavaborole, a novel, boron-based pharmaceutical agent: phase 2 studies conducted for the topical treatment of toenail onychomycosis.

OBJECTIVE: To assess the potential efficacy, safety, and optimal dosing concentration of tavaborole, a novel, boron-based pharmaceutical agent with broad-spectrum antifungal activity, for the treatment of onychomycosis of the toenail due to dermatophytes. METHODS: One double-blind, randomized, vehicle-controlled study (study 1) and two open-label studies (studies 2 and 3) examined the efficacy, safety, and optimal dosing concentration of tavaborole topical solution applied once daily or three times weekly for 180 days at concentrations of 1.0%, 2.5%, 5.0%, or 7.5%. Patient cohort 3 of study 2 received open-label tavaborole 5.0% once daily for 360 days. All three studies assessed day 180 treatment success, defined as complete or partial clinical evidence of clear nail growth plus negative fungal culture. RESULTS: A total of 336 patients were included in the intent-to-treat (ITT) or modified ITT populations and efficacy analyses across the 3 studies. In study 1, treatment success rates at day 180 were higher with tavaborole 2.5%, 5.0%, and 7.5% vs vehicle (27%, 26%, and 32% vs 14%, respectively; slope P=0.030). In cohort 3 of study 2, 7% of patients achieved treatment success with tavaborole 5.0% at day 360. Negative culture rates at day 180 in study 1 were numerically higher for tavaborole 2.5%, 5.0%, and 7.5% vs vehicle (slope P=0.046). Application-site reactions of general irritation, erythema, scaling, and stinging/burning were most common with tavaborole 7.5%, were generally mild to moderate, and resolved with treatment discontinuation and/or a reduction in dosing frequency. No systemic safety concerns were observed. CONCLUSION: Tavaborole solution demonstrated favorable efficacy and safety in phase 2 clinical studies. Based on these findings, tavaborole topical solution, 5% was further investigated in larger, more definitive phase 3 studies. Results from these completed phase 3 studies will provide additional evidence regarding the safety and efficacy of tavaborole in the treatment of toenail onychomycosis.

Treatment of Fordyce spots with CO2 laser.

BACKGROUND: Fordyce spots are heterotopic sebaceous glands that can be located at the lips' vermilion or the oral mucosa. Although this is considered a rather common disorder, a treatment for this condition that sometimes affects patients from only a cosmetic viewpoint has not yet been described. OBJECTIVE: To evaluate CO2 superpulsed laser treatment in two subjects with Fordyce spots. METHODS: Two patients with papules and yellowish plaques at the upper lip corresponding to Fordyce spots were treated with coherent Ambulase CO2 superpulsed laser (Coherent Medical, Palo Alto, CA); after informed consent was obtained, two to three passes were performed in one session using 2 and 4 W and a spot size of 2 mm. RESULTS: Complete re-epithelization was observed 2 weeks later with no residual Fordyce papules in the treated area and no side effects. CONCLUSION: Our findings suggest that CO2 superpulsed laser can be considered a safe and effective treatment for patients with Fordyce spots, offering excellent cosmetic results.