University of California, Davis

Once abandoned because of devastating teratogenic effects, thalidomide has reemerged as an alternative treatment in many dermatologic diseases. In 1998, thalidomide became FDA approved for the acute treatment and suppression of the cutaneous manifestations of erythema nodosum leprosum (ENL). ENL is a systemic disorder that typically occurs after several years of antileprosy treatments, usually for lepromatous leprosy. Off-label uses for thalidomide include: aphthous stomatitis, Behçet disease, pyoderma gangrenosum, chronic discoid lupus erythematosus, systemic lupus erythematosus, lichen planus, prurigo nodularis and sarcoidosis. This review examines the background, pharmacokinetics, mechanism of action, side-effects, and indications of thalidomide.

Severe skin adverse drug reactions can result in death. Toxic epidermal necrolysis (TEN) has the highest mortality (30-35%); Stevens-Johnson syndrome and transitional forms correspond to the same syndrome, but with less extensive skin detachment and a lower mortality (5-15%). Hypersensitivity syndrome, sometimes called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), has a mortality rate evaluated at about 10%. Drug reactions are self-limited diseases and therefore, generally treatment is symptomatic. Prompt diagnosis, identification of, and early withdrawal of all suspect drugs are the most important preliminaries. The management of the patients must be undertaken in specialized intensive care units, with the same main types of therapy as for burns: warming of the environment, correction of electrolyte disturbances, administration of a high caloric enteral intake, and prevention of sepsis. Efficacy of drugs used in some case reports is difficult to evaluate: intravenous immunoglobulins, cyclosporin, cyclophosphamide, pentoxyfilline, and thalidomide have all been tried. Corticosteroid use is debated and is probably deleterious in late forms of TEN. For DRESS, corticoids are used in cases of life-threatening systemic impairment. Specific nursing care and adequate topical management reduce associated morbidity and allow a more rapid re-epithelialization of skin lesions. After healing, follow-up is needed for ophthalmologic and mucous membrane sequelae. Sunblocks are recommended. Testing for glycemia must be done. Avoidance of the responsible drug and chemically related compounds is essential for the patient and first-degree relatives.

Keloid formation occurs as a result of abnormal wound healing. Despite the high prevalence of keloids in the general population, they remain one of the more challenging dermatologic conditions to manage. More than a cosmetic nuisance, they are often symptomatic and can have a significant psychosocial burden for the patient. Although multiple treatment modalities exist, no single treatment has proven widely effective. In fact, recurrence following treatment is generally the norm. Combination therapy is likely the optimal strategy. In this review, we highlight the clinical features, pathophysiology and management of keloids.

Although the delayed type hypersensitivity (DTH) reaction was discovered over 100 years ago, the exact nature of the reaction has been the subject of contentious debate over the years. The reaction was discovered in 1882 by Robert Koch, but it was not until the 1940s that Landsteiner and Chase proved that the reaction was mediated by the cellular and not the humoral arm of the immune system. The first DTH reaction described used only the tuberculin antigen (tuberculin reaction), but the definition was later expanded to include cell mediated reactions to other bacterial and viral antigens, responses to pure protein with adjuvant or haptens, and host responses to allograft. The DTH skin test is used to test if prior exposure to an antigen has occurred. When small quantities of antigen are injected dermally, a hallmark response is elicited which includes induration, swelling and monocytic infiltration into the site of the lesion within 24 to 72 hours. This reaction has been shown to be absolutely dependent on the presence of memory T cells. Both the CD4+ and CD8+ fractions of cells have been shown to modulate a response. Contemporary debate regarding the reaction is focused on the role of the Th1 and Th2 cells originally discovered by Mosmann. It has been postulated that the Th1 cell is the "inducer" of a DTH response since it secretes interferon gamma (IFN ), a potent stimulator of macrophages, while the Th2 cell is either not involved or acting as a downregulator of the cell mediated immune response. Despite the early experimental success of this theory, experiments have shown that Th2 cells may be involved in certain types of proinflammatory cell mediated immunity. This review focuses on the nature of the different forms of DTH that can be elicited and the different experimental evidence that has led to the current theories regarding DTH and its role in cell mediated immunity.

There has been a remarkable paucity of evidence for an association between diet and acne. Our previous studies suggest that there is an association between milk intake and teenage acne. This is a prospective cohort study to evaluate that relationship. We studied 6,094 girls, aged 9-15 years in 1996, who reported dietary intake on up to three food frequency questionnaires from 1996 to 1998. Presence and severity of acne was assessed by questionnaire in 1999. We computed multivariate prevalence ratios (PR) and 95 percent confidence intervals for acne. After accounting for age at baseline, height and energy intake, the multivariate PRs (95 % CI; p-value for test of trend) for acne comparing highest (2 or more servings per day) to lowest (<1 per week) intake categories in 1996, were 1.20 (1.09, 1.31; <0.001) for total milk, 1.19 (1.06, 1.32; <0.001) for whole milk, 1.17 (1.04, 1.31; 0.002) for low fat milk and 1.19 (1.08, 1.31; <0.001) for skim milk. This result did not change appreciably when we excluded girls who reported use of contraceptives and when we restricted our analysis to those younger than 11 years of age at baseline. We found a positive association between intake of milk and acne. This finding supports earlier studies and suggests that the metabolic effects of milk are sufficient to elicit biological responses in consumers.

INTRODUCTION: Acne is a significant adolescent problem and may precipitate emotional and psychological effects. The impact of acne on psychological parameters and implications for acne treatment are not fully understood. METHODS: We performed a MEDLINE search using the terms "acne" and "adolescent" along with "psychological," "depression," or "psychiatric," which yielded 16 reviewed studies. RESULTS: Qualitative review of the selected articles revealed that the presence of acne has a significant impact on self-esteem and quality of life. Depression and other psychological disorders are more prevalent in acne patients and acne treatment may improve symptoms of these disorders. LIMITATIONS: The reviewed studies were semi-quantitative analyses utilizing various standardized surveys or questionnaires. Therefore, quantitative analysis of selected studies was not possible. CONCLUSION: The presence of co-morbid psychological disorders should be considered in the treatment of acne patients and future prospective trials are needed to assess the impact of treatment on psychological outcomes.

Erythema multiforme (EM) is a clinical conundrum the name of which reflects the broad morphological spectrum of the lesions. Molecular and immunologic evidence that herpes simplex virus (HSV) causes a subset of EM lesions [herpes-associated EM (HAEM)] is reviewed, and new data are presented which suggest that autoreactive T-cells triggered by virus infection play an important role in HAEM pathogenesis. Disease development begins with viral DNA fragmentation and the transport of the DNA fragments to distant skin sites by peripheral blood mononuclear cells (PBMCs). HSV genes within DNA fragments deposited on the skin [notably DNA polymerase (Pol)] are expressed, leading to recruitment of HSV-specific CD4+ Th1 cells that respond to viral antigens with production of interferon-gamma (IFN-gamma). This step initiates an inflammatory cascade that includes expression of IFN-gamma induced genes, increased sequestration of circulating leukocytes, monocytes and natural killer (NK) cells, and the recruitment of autoreactive T-cells generated by molecular mimicry or the release of cellular antigens from lysed cells. The PBMCs that pick up the HSV DNA [viz. macrophages or CD34+ Langerhans cells (LC) precursors], their ability to process it, the viral proteins expressed in the skin and the presence of epitopes shared with cellular proteins may determine whether a specific HSV episode is followed by HAEM development. Drug-associated EM (DIEM) is a mechanistically distinct EM subset that involves expression of tumor necrosis factor alpha (TNF-alpha) in lesional skin. It is our thesis that the polymerase chain reaction (PCR) assay for HSV DNA detection in lesional skin and staining with antibodies to IFN-gamma and TNF-alpha, are important criteria for the diagnosis of skin eruptions and improved patient management.

Acanthosis nigricans is a dermatosis characterized by thickened, hyperpigmented plaques, typically of the intertriginous surfaces and neck. Common in some populations, its prevalence depends on race. Clinicians should recognize acanthosis nigricans; it heralds disorders ranging from endocrinologic disturbances to malignancy. In this review, we discuss the pathogenesis of acanthosis nigricans and its clinical implications and management.

Imiquimod is a novel synthetic compound that is a member of the imidazoquinolone family of drugs. This class of drugs, which also includes a more potent member, resimiquimod (R-848), is unique having the properties of topical immune response modifiers and stimulators. Imiquimod resembles a nucleoside analogue and is known for its potent induction of endogenous antiviral pro-inflammatory mediators. This article is a review of the relevant literature as it relates to the off-label applications of imiquimod 5 percent cream for treatment of cutaneous preneoplastic and neoplastic conditions including its recently approved indication for treating actinic keratoses.

Background: Bullous pemphigoid (BP) is a chronic autoimmune blistering disease that disproportionately affects older adults and is associated with substantial morbidity, mortality, and treatment-related risks. Despite an expanding therapeutic landscape, real-world prescribing patterns in this population remain poorly characterized. Objective: To evaluate medication prescribing patterns among older adults with BP and assess the feasibility of using national claims data to characterize treatment exposures relevant to drug safety and risk stratification. Methods: We conducted a retrospective cohort study using Medicare fee-for-service claims data (2016-2020). Adults aged 65 years or older with BP were identified using ICD-10 codes. Prescription drug event data were linked to outpatient claims to capture medication use. Treatments were categorized into topical corticosteroids (by potency), oral immunomodulators and antibiotics, and biologic therapies. Descriptive analyses were performed to evaluate prescribing distributions. Results: Among 10,959 patients with BP and 78,468 outpatient claims, we identified 19,663 prescriptions. Oral immunomodulators and antibiotics comprised 67.5% of prescriptions, followed by topical corticosteroids (32.5%) and biologics (0.04%). Prednisone accounted for 62.9% of oral prescriptions, followed by doxycycline (20.2%) and mycophenolate (6.0%). Among topical steroids, medium-potency agents were most common (40.6%), followed by super high-potency (38.2%). Biologic use was rare, with dupilumab accounting for most prescriptions. Conclusion: Systemic corticosteroids remain the predominant therapy for BP in older adults, with substantial variability in topical steroid use and minimal uptake of biologics. These findings highlight gaps in treatment optimization and support the need for risk-informed, steroid-sparing strategies in this high-risk population.

Background: Cutaneous lupus erythematosus (CLE) is associated with high symptomatic burden and sustained activation of immune pathways, notably type I interferon (IFN-I) and tumor necrosis factor-alpha (TNF-α). In patients refractory to standard treatments, such as photoprotection, corticosteroids, antimalarials, and immunomodulators, targeted therapies have emerged as potential alternatives. Objective: To assess the efficacy and safety of targeted therapies against IFN-I or TNF-α compared to standard treatments in patients with CLE. Methods: A systematic review was conducted of randomized controlled trials (RCTs) involving adults or adolescents with CLE (with or without systemic lupus erythematosus), reporting cutaneous outcomes (CLASI-A, CLASI-50, responder rates) and safety. Literature searches were performed in MEDLINE, Embase, and LILACS without language restrictions. Risk of bias was evaluated using the Cochrane RoB 2 tool. Owing to clinical heterogeneity, results were synthesized narratively. Results: Eight RCTs met inclusion criteria, predominantly evaluating IFN-I pathway inhibitors. Anifrolumab showed significant benefit in TULIP-2 (CLASI-50: 49% vs 25%; P = .001) and MUSE (63% vs 30.8%). Sifalimumab achieved CLASI-50 responses up to 73%. Deucravacitinib (TYK2 inhibitor) and BIIB059 (anti-BDCA2) also showed clinical improvements. RSLV-132 and epratuzumab did not demonstrate efficacy. IFN-I blockade was associated with increased viral infections, particularly herpes zoster. Two studies were rated as high risk of bias; the remainder presented some concerns. Conclusion: Targeted inhibition of IFN-I and TYK2 pathways appears effective in reducing cutaneous activity in CLE, with acceptable safety profiles. Evidence for anti-TNF therapies remains insufficient. Further trials stratified by CLE subtype and patient-reported outcomes are warranted to inform clinical guidelines.

Background: Inflammatory skin diseases, including psoriasis and atopic dermatitis, require long-term management strategies that balance efficacy with safety. The 2025 American Academy of Dermatology guidelines encourage the judicious application of topical corticosteroids when their use is deemed necessary and for short durations of therapy. Recent availability of newer nonsteroidal topical therapies that are effective and safe, including for prolonged durations and on sensitive skin sites, has prompted a need for evidence-based guidance for clinicians in real-world practice. Tapinarof, a first-in-class, nonsteroidal aryl hydrocarbon receptor (AhR) agonist, was approved by the US Food and Drug Administration for the treatment of plaque psoriasis in adults and atopic dermatitis in patients aged 2 years and older in 2022 and 2025, respectively; however, its optimal place in therapy remains to be established. Objective: To develop expert consensus statements on the role of AhR agonists in the management of inflammatory skin diseases. Methods: A literature search produced 31 articles meeting inclusion criteria that were independently reviewed by an 11-member expert panel that convened on January 19, 2026. A modified Delphi process was used to develop 9 consensus statements. Consensus Recommendations / Key Findings: AhR agonists represent a distinct therapeutic class with a unique multimodal mechanism involving immune modulation across Th1/Th2/Th17/Th22 pathways, skin barrier normalization, and antioxidant activity; tapinarof demonstrates a favorable safety profile with no restrictions on anatomic site, body surface area, or duration of use; tapinarof may be used concomitantly with systemic therapies; tapinarof is appropriate as both initial and long-term therapy for psoriasis in adults and atopic dermatitis in patients aged 2 years and older; and nonsteroidal topical therapies are preferred for chronic inflammatory skin diseases, particularly on the face and intertriginous areas. Conclusion: AhR agonist therapy offers a clinically meaningful, advanced nonsteroidal option that addresses key limitations of traditional topical therapies in inflammatory skin disease management.

Background: Dermoscopy is an essential diagnostic tool in dermatology; however, its application in patients with dark skin phototypes remains insufficiently explored. Objective: To assess dermatologists' practices, perceptions, and challenges regarding dermoscopy use in Fitzpatrick skin phototypes IV to VI. Methods: We conducted a cross-sectional study between February and May 2025. An online questionnaire was distributed to dermatologists practicing in various professional settings. A total of 64 participants were included. Results: Although dermoscopy was widely used, heterogeneous practices and a lack of structured training were identified. The main difficulties involved the interpretation of pigmented lesions, particularly melanoma, and the reduced visibility of vascular structures. Most respondents reported a lack of standardized criteria and adapted educational resources. Conclusion: These findings highlight the need for dedicated training programs and a more inclusive approach to dermoscopy in patients with dark skin.

Background: Chronic and treatment-resistant dermatologic disorders remain difficult to manage with current therapies because of incomplete efficacy, tolerability limitations, and long-term safety concerns. GZ21T is a topical formulation of curcumin, harmine, and isovanillin that has emerged as a potential novel therapy for inflammatory and neoplastic skin disease. Objective: To review the preclinical evidence, proposed mechanism of action, safety data, and future clinical potential of GZ21T in atopic dermatitis, mycosis fungoides, and actinic keratoses. Methods: A focused literature review was performed using published preclinical and early translational studies evaluating GZ17-6.02 and topical GZ21T in dermatologic disease models, including atopic dermatitis, mycosis fungoides, and actinic keratoses. Studies were included if they reported mechanistic, efficacy, or safety outcomes relevant to dermatologic application; non-dermatologic studies were used selectively to contextualize safety and pharmacology. Results: Across preclinical models, topical GZ21T reduced inflammation, pruritus, lesion burden, and tumor growth while promoting autophagy and suppressing pro-survival signaling pathways including MAPK, PI3K-AKT, mTOR-related pathways, Wnt, and ERBB signaling. In mycosis fungoides models, GZ17-6.02 increased apoptosis and enhanced tumor cell killing, including in combination with standard agents such as bexarotene. Safety data to date suggest favorable local tolerability, minimal systemic absorption in preclinical topical studies, and reversible liver enzyme elevations in oral phase 1 testing of GZ17-6.02. Conclusion: GZ21T represents a promising topical, multimodal therapeutic approach for inflammatory and premalignant or malignant skin disease. Further clinical studies are needed to confirm efficacy, define long-term safety, and establish its role relative to current standard therapies.

Topical glycopyrrolate 0.5% solution effectively reduced multiple periorbital and facial eccrine hidrocystomas with rapid improvement and no adverse effects, offering a novel non-surgical therapeutic option.This case supports glycopyrrolate as a well-tolerated alternative for managing multiple eccrine hidrocystomas and highlights the need for standardized treatment guidelines in this challenging condition.

We present a case of leg-type diffuse large-cell lymphoma of the nasal area successfully treated with contact radiotherapy.This case demonstrates that in cases involving atypical locations where surgery is not feasible and chemotherapy is not possible, contact radiation therapy can be performed.

This case describes a rare coincidental finding of eccrine angiomatous hamartoma (EAH) presenting as a new asymptomatic, nondescript, erythematous patch at an annual skin exam.The coincidental finding of asymptomatic EAH at a routine exam highlights the potential for this condition to be underdiagnosed.