Depressive symptoms, depression, and the effect of biologic therapy among patients in Psoriasis Longitudinal Assessment and Registry (PSOLAR)
Strober, Bruce; Gooderham, Melinda; de Jong, Elke M G J; Kimball, Alexa B; Langley, Richard G; Lakdawala, Nikita; Goyal, Kavitha; Lawson, Fabio; Langholff, Wayne; Hopkins, Lori; Fakharzadeh, Steve; Srivastava, Bhaskar; Menter, Alan
BACKGROUND:Patients with psoriasis are at an increased risk for depression. However, the impact of treatment on this risk is unclear. OBJECTIVE:Evaluate the incidence and impact of treatment on depression among patients with moderate-to-severe psoriasis. METHODS:We defined a study population within the Psoriasis Longitudinal Assessment and Registry and measured the incidence of depressive symptoms (Hospital Anxiety and Depression Scale-Depression score â‰¥8) and adverse events (AEs) of depression within cohorts receiving biologics, conventional systemic therapies, or phototherapy. Patients were evaluated at approximately 6-month intervals. Multivariate modeling determined the impact of treatment on risk. RESULTS:The incidence rates of depressive symptoms were 3.01 per 100 patient-years (PYs) (95% confidence interval [CI], 2.73-3.32), 5.85 per 100 PYs (95% CI, 4.29-7.97), and 5.70 per 100 PYs (95% CI, 4.58-7.10) for biologics, phototherapy, and conventional therapy, respectively. Compared with conventional therapy, biologics reduced the risk for depressive symptoms (hazard ratio, 0.76; 95% CI, 0.59-0.98), whereas phototherapy did not (hazard ratio, 1.05; 95% CI, 0.71-1.54). The incidence rates for AEs of depression were 0.21 per 100 PYs (95% CI, 0.15-0.31) for biologics, 0.55 per 100 PYs (95% CI, 0.21-1.47) for phototherapy, and 0.14 per 100 PYs (95% CI, 0.03-0.55) for conventional therapy; the fact that there were too few events (37 AEs) precluded modeling. LIMITATIONS/CONCLUSIONS:Incomplete capture of depression and confounders in the patients on registry. CONCLUSION/CONCLUSIONS:Compared with conventional therapy, biologics appear to be associated with a lower incidence of depressive symptoms among patients with psoriasis.
Vasculitis: Kids are not just little people
Lakdawala, Nikita; Fedeles, Flavia
Cutaneous vasculitis, inflammatory destruction of blood vessels, can present with a wide range of clinical and pathologic findings across a number of heterogeneous conditions. Although some vasculitides are present in both children and adults, some important differences exist in clinical presentation, etiology, management, and prognosis in childhood vasculitis versus adult vasculitis. Cutaneous vasculitis is rare in children, and most childhood vasculitides, of which Henoch-SchÃ¶nlein purpura is the most common, histologically are small vessel leukocytoclastic vasculitis. In children, infectious etiologies are more common than in adults. Childhood cutaneous vasculitis is most often self-limited with a good prognosis, and treatment is mainly supportive. Â© 2017 Elsevier Inc. All rights reserved.
Granulomatous diseases: Kids are not just little people
Lakdawala, Nikita; Ferenczi, Katalin; Grant-Kels, Jane M
Granulomatous diseases represent a heterogeneous group of conditions characterized by histiocytic inflammation that affect patients of any age. These diseases differ widely in their pathogenesis and include infectious and noninfectious conditions. This review focuses on noninfectious granulomatous conditions, with particular emphasis on age-related differences in the onset, epidemiology, clinical manifestations, prognosis, and age-specific management of specific granulomatous disorders. Knowledge of age-specific aspects of granulomatous conditions in adults and children improves both the extent of the diagnostic workup and the management of these patients.
The "bumpy" adolescent nose: Acne associated angiofibroma-like nasal papules
Roman, Jorge; Krueger, Loren D; Young, Trevor K; Rieder, Evan A; Rothman, Lisa R; Lakdawala, Nikita; Nagler, Arielle R; Meehan, Shane A; Orlow, Seth J; Oza, Vikash S
BACKGROUND/OBJECTIVE/OBJECTIVE:Papular scars are a recently described clinical phenotype of acne scarring characterized by papules occurring on the nose and chin. We have observed a similar presentation of nasal papules among patients seen in our clinic for acne and sought to further characterize the clinical and histopathological characteristics of this entity. METHODS:In this single-site case series, a retrospective review of electronic medical records of patients with nasal papules in association with acne vulgaris between April 2018 and April 2019 was performed. Clinical and histopathologic findings were recorded. RESULTS:We identified 20 patients who presented with a similar clinical phenotype of predominantly skin-colored, dome-shaped papules concentrated on the nose and chin in association with a history of more classic facial acne vulgaris. Papular lesions were seen predominately in adolescent Hispanic males. Concomitant acne on other areas of the face was identified in 18 patients at presentation while two patients had a history of adolescent acne. Biopsies were performed for five patients. Histopathologic examination demonstrated features of fibrosis and dilated thin-walled blood vessels, typical of angiofibromas. CONCLUSION/CONCLUSIONS:We present a series of adolescent patients with large, flesh-colored to erythematous papules seen predominantly on the nose. These lesions are histologically indistinguishable from angiofibromas and may represent an under-recognized yet disfiguring sequela of acne that may disproportionately affect adolescents with skin of color.
Dabrafenib-induced neutrophilic panniculitis in a child undergoing dual BRAF-MEK inhibitor therapy for glioblastoma multiforme
Young, Trevor K; Gutierrez, Daniel; Criscito, Maressa C; Kim, Randie H; Lakdawala, Nikita; Oza, Vikash S
BRAF inhibitor-induced neutrophilic panniculitis is a rare event that is well-characterized in adults undergoing therapy for metastatic melanoma. To date, there are very few reports of this event in children undergoing BRAF inhibitor therapy for low-grade gliomas, all of which were seen with vemurafenib. We report a case of dabrafenib-induced neutrophilic panniculitis in a 9-year-old girl that manifested within several weeks of initiating dual BRAF-MEK inhibitor therapy for glioblastoma multiforme. This case highlights neutrophilic panniculitis as a side effect of dabrafenib in children and serves as a reminder to consider cutaneous side effects of BRAF inhibitors as they are increasingly used to treat children with primary brain tumors.
Targeted Inhibition of the Epidermal Growth Factor Receptor and Mammalian Target of Rapamycin Signaling Pathways in Olmsted Syndrome
Zhang, April; Duchatelet, Sabine; Lakdawala, Nikita; Tower, Richard L; Diamond, Carrie; Marathe, Kalyani; Hill, India; Richard, Gabriele; Diab, Yaser; Kirkorian, Anna Yasmine; Watanabe, Flora; Siegel, Dawn H; Hovnanian, Alain
Importance/UNASSIGNED:Olmsted syndrome is a rare and disabling genodermatosis for which no successful treatment is currently available. Objective/UNASSIGNED:To evaluate the clinical response to the mammalian target of rapamycin (mTOR) inhibitor sirolimus and/or the epidermal growth factor receptor (EGFR) inhibitor erlotinib among patients with Olmsted syndrome. Design, Setting, and Participants/UNASSIGNED:This case series focused on 4 children with treatment-refractory Olmsted syndrome. These children received treatments (initiated in 2017 and 2018) at the outpatient dermatology clinic at the Children's Hospital of Wisconsin in Milwaukee, Wisconsin; Children's National Hospital in Washington, DC; and Hospital Infantil Pequeno PrÃncipe, Curitiba in ParanÃ¡, Brazil. Exposures/UNASSIGNED:Immunohistochemical analyses for mTOR and EGFR activation were performed on skin biopsy specimens from 2 patients. Oral sirolimus was administered to these 2 patients at a dosage of 0.8 mg/m2 twice daily, titrated to a goal trough whole-blood concentration of 10 to 15 ng/mL. Erlotinib was administered to all 4 patients at a dosage of 2 mg/kg/d. Main Outcomes and Measures/UNASSIGNED:Clinical responses were assessed with visual analog scales for pruritus and pain and/or the Children's Dermatology Life Quality Index. Adverse effects were monitored throughout treatment. Results/UNASSIGNED:Four patients (mean [SD] age, 7  years; 2 boys and 2 girls) were analyzed. Lesional skin immunostaining showed increased phosphorylated ribosomal protein S6 (RPS6) and phosphorylated EGFR staining in the epidermis, indicating enhanced mTOR and EGFR signaling activation. Patients 1 and 2 were initially treated with sirolimus, displaying substantial clinical improvement in erythema and periorificial hyperkeratosis afterward. When switched to erlotinib, these patients showed substantial palmoplantar keratoderma (PPK) improvement. Patients 3 and 4 were treated with erlotinib only and later showed rapid and near complete resolution of PPK and substantial improvement in Children's Dermatology Life Quality Index scores. All 4 patients had sustained improvements in pruritus and pain. No severe adverse effects were reported. Conclusions and Relevance/UNASSIGNED:This study's findings suggest that the EGFR-mTOR cascade may play a substantial role in the pathophysiological process of Olmsted syndrome and may serve as a major therapeutic target. Oral sirolimus and erlotinib may be a promising, life-altering treatment for pediatric patients with Olmsted syndrome.
Diffuse papulopustular eruption in a newborn
Lakdawala, Nikita; Humphrey, Stephen R
Depressive symptoms, depression, and the effect of systemic therapy among patients in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) [Meeting Abstract]
Strober, Bruce; Lakdawala, Nikita; de Jong, Elke; Gooderham, Melinda; Goyal, Kavitha; Langholff, Wayne; Srivastava, Bhaskar; Menter, Alan
Acrodermatitis caused by nutritional deficiency and metabolic disorders
Lakdawala, Nikita; Grant-Kels, Jane M
Both the metabolism and dietary intake of vitamins and minerals are essential to homeostatic function in the body. Dietary excess or deficiency, as well as genetic and acquired disorders in metabolism, can present dermatologically and systemically. More specifically, disorders in metabolism of zinc, biotin, essential fatty acids, and vitamin B, can appear with acrally distributed dermatoses. Recognition of the dermatologic manifestations associated with nutritional disorders is important for early diagnosis and management.
Multiculturalism and diversity: How to ethically care for a prejudiced patient
Shahriari, Neda; Lakdawala, Nikita; Grant-Kels, Jane M