Evidence-Based Clinical Practice Guidelines for Laser-Assisted Drug Delivery.

Importance: Laser-assisted drug delivery (LADD) is used for various medical and cosmetic applications. However, there is insufficient evidence-based guidance to assist clinicians performing LADD. Objective: To develop recommendations for the safe and effective use of LADD. Evidence Review: A systematic literature review of Cochrane Central Register of Controlled Trials, Embase, and MEDLINE was conducted in December 2019 to identify publications reporting research on LADD. A multidisciplinary panel was convened to draft recommendations informed by the systematic review; they were refined through 2 rounds of Delphi survey, 2 consensus meetings, and iterative review by all panelists until unanimous consensus was achieved. Findings: Of the 48 published studies of ablative fractional LADD that met inclusion criteria, 4 were cosmetic studies; 21, oncologic; and 23, medical (not cosmetic/oncologic), and 6 publications of nonablative fractional LADD were included at the request of the expert panel, producing a total of 54 studies. Thirty-four studies (63.0%) were deemed to have low risk of bias, 17 studies (31.5%) had moderate risk, and 3 (5.5%) had serious risk. The key findings that informed the guidelines developed by the expert panel were as follows: LADD is safe in adults and adolescents (≥12 years) with all Fitzpatrick skin types and in patients with immunosuppression; it is an effective treatment for actinic keratosis, cutaneous squamous cell carcinoma in situ, actinic cheilitis, hypertrophic scars, and keloids; it is useful for epidermal and dermal analgesia; drug delivery may be increased through the application of heat, pressure, or occlusion, or by using an aqueous drug solution; laser settings should be selected to ensure that channel diameter is greater than the delivered molecule; antibiotic prophylaxis is not recommended, except with impaired wound healing; antiviral prophylaxis is recommended when treating the face and genitalia; and antifungal prophylaxis is not recommended. The guideline's 15 recommendations address 5 areas of LADD use: (I) indications and contraindications; (II) parameters to report; (III) optimization of drug delivery; (IV) safety considerations; and (V) prophylaxis for bacterial, viral, and fungal infections. Conclusions and Relevance: This systematic review and Delphi consensus approach culminated in an evidence-based clinical practice guideline for safe and effective use of LADD in a variety of applications. Future research will further improve our understanding of this novel treatment technique.

A Diagnostic Approach to Recurrent Orofacial Swelling: A Retrospective Study of 104 Patients.

OBJECTIVE: To identify patients evaluated in an outpatient setting at our institution with a presentation of recurrent orofacial swelling and to review the spectrum of causes to outline a diagnostic approach. PATIENTS AND METHODS: A retrospective study of 104 patients with more than 1 episode of orofacial swelling lasting for more than 5 days identified through a keyword search of the electronic health record from January 2, 2000, through July 5, 2011. RESULTS: Patients were categorized according to final cause of orofacial swelling: idiopathic orofacial granulomatosis, solid facial edema due to rosacea and acne vulgaris, Crohn disease, contact dermatitis, sarcoidosis, exfoliative cheilitis, lichen planus, actinic cheilitis, cheilitis glandularis, lymphedema, miscellaneous, and multifactorial. Granulomatous inflammation was noted on biopsy in 40 of 85 patients (47%). Oral involvement was associated with Crohn disease (P<.001), and facial and periorbital swelling was associated with solid facial edema in the setting of rosacea and acne vulgaris (P<.001). CONCLUSION: The broad range of diagnoses responsible for recurrent orofacial swelling underscores the diagnostic challenge and importance of a thorough multidisciplinary evaluation to identify underlying causes.

Isotretinoin for acne and rosacea.

Isotretinoin is a revolutionary medicine for the treatment of acne vulgaris, with new studies showing evidence of excellent clinical outcomes in treating rosacea. After 30 years of clinical experience, new insights are being gained into dosing strategies, recurrence prevention, and dose-related side effects. Previous controversial associations with inflammatory bowel diseases and mood disorders have hampered the use of this medication in some clinical situations, with new evidence disproving these claims. The teratogenicity of this medication mandates iPLEDGE compliance with government regulations. Clinicians should be knowledgeable about this medication including its side effects, teratogenicity, and its controversies in order to adequately counsel patients, dissuade fears, and obtain the best clinical outcome when treating acne and rosacea.

Orofacial granulomatosis.

Orofacial granulomatosis (OFG) is an uncommon chronic granulomatous condition with a multifactorial etiology and pathogenesis. Genetic, immunologic, allergic, and infectious mechanisms have been implicated. OFG is often used as a descriptor to encompass all entities with orofacial swelling and histologic evidence of noncaseating granulomas. The diagnosis of OFG should prompt evaluation for provocative factors. The cause of most cases of OFG remains obscure. The clinician must consider mycobacterial infections, deep fungal infections, sarcoidosis, rosacea, and Crohn disease (CD). In addition, OFG should be considered synonymous with previously described conditions, including granulomatous cheilitis and Miescher cheilitis, as well as Melkersson-Rosenthal syndrome and its monosymtomatic or oligosymptomatic variants. The relationship of OFG to CD is currently debated, with recent evidence suggesting the possibility of three entities: classic oral CD (established gastrointestinal CD with oral involvement), OFG with gastrointestinal involvement (OFG with subclinical or asymptomatic gastrointestinal endoscopy changes), and OFG without bowel involvement. Childhood onset, presence of certain phenotypic features, laboratory abnormalities, or gastrointestinal symptoms may indicate the need for further evaluation to assess for concurrent or future CD. Although multiple therapies have been found to be effective in small numbers of patients, treatment should be tailored to each patient.

The coexistence of peripheral nerve sheath tumors and vitiligo: more than coincidence?

Neurocristopathies arise from abnormal migration, differentiation, or proliferation of neural crest derivatives, leading to diverse clinical and pathological features. They are classified into dysgenetic or neoplastic, and can affect single or multiple sites (simple versus complex). Examples include congenital melanocytic nevi, neuroblastoma, Hirshsprung's disease, Waardenburg's syndrome, neurofibromatosis (NF) 1 and multiple endocrine neoplasia (MEN) 2A and 2B. We report two cases of peripheral nerve sheath tumors associated with vitiligo and discuss the possible implicated embryologic, genetic and molecular mechanisms. To our knowledge, we also report the first case of de novo malignant peripheral nerve sheath tumor (MPNST) associated with vitiligo.

Cutaneous manifestations in patients with POEMS syndrome.

BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome is a rare multisystem paraneoplastic condition associated with plasma cell dyscrasia. METHODS: From our institution's dysproteinemia database, 107 patients met criteria for polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome between January 1, 2000, and October 1, 2009. Medical records were reviewed for documented syndrome features at diagnosis. We assessed prevalence of skin findings and associations between dermatologic and other characteristic disease findings. RESULTS: Of the 107 patients, 96 (90%) had a recognized cutaneous manifestation. Hyperpigmentation and hemangioma were most common (47%), followed by hypertrichosis (38%). Vascular skin changes--acrocyanosis (34%), Raynaud phenomenon (20%), hyperemia/erythema (20%), flushing (16%), or rubor (11%)--occurred in 62%; white nails, sclerodermoid changes, and clubbing occurred in 30%, 26%, and 6%, respectively. Mean number of skin findings per patient was 2.9 (median, 3.0; range, 0-7). Presence of cutaneous manifestation was associated with abnormal pulmonary function tests (P < 0.001); immunoglobulin G gammopathy was associated with hyperpigmentation and hypertrichosis. No other significant associations were seen. CONCLUSIONS: The high prevalence of skin findings (90%) shows the value of dermatologic evaluation in diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. Our data indicate new associations between skin findings and other disease characteristics.