Saisindhu Narala, MD, MAS

All Publications

• Histopathologic and Clinical Characterization of Brentuximab Vedotin-associated Rash. The American journal of surgical pathology Narala, S., Saleem, A., Brown, R. A., Novoa, R. A., Kim, Y. H., Rieger, K. E. 2024

  Abstract

  Rash is one of the commonly observed adverse events with brentuximab vedotin (BV), a CD30-targeted antibody-drug conjugate used to treat cutaneous T-cell lymphoma (CTCL). However, clinical and histopathologic characterization of BV-associated rash (BVAR) is limited. Distinguishing BVAR from a patient's underlying CTCL can be challenging and can lead to treatment interruptions or even premature drug discontinuation. We performed a thorough clinical and histopathologic retrospective characterization of BVAR from a single institution. Utilizing polymerase chain reaction (PCR) and T-cell receptor high-throughput sequencing (TCR-HTS), we were able to isolate skin biopsy specimens from rash clinically suggestive of BVAR that also lacked a dominant TCR clone. A retrospective evaluation was performed of 26 biopsy specimens from 14 patients. Clinical features of BVAR included predominantly morbilliform or maculopapular morphology, delayed onset, and the trend toward moderate to severe classification, often requiring oral steroids. Most histopathologic specimens (25/26) showed spongiotic dermatitis as the primary reaction pattern. Many cases showed subtle findings to support a background interface or lichenoid eruption. Langerhans cell microabscesses were seen in one-fourth of specimens, and eosinophils were present in over one-half of the specimens. There were focal features mimicking CTCL, but these were not prominent. In 17 specimens with immunohistochemistry, the CD4:CD8 ratio in intraepidermal lymphocytes was relatively normal (1-6:1) in 65% (11/17) and 1:1 in 35% (6/17), demonstrating a trend toward increased CD8-positive cells compared with baseline CTCL. We have identified features that can help distinguish BVAR from a patient's CTCL, which can, in turn, help guide appropriate clinical management.

  View details for DOI 10.1097/PAS.0000000000002268

  View details for PubMedID 38907612

• Primary Cutaneous CD30+Large T Cell Lymphoproliferative Disorder Associated With Prolonged Exposure to Fingolimod Cooper, J., Soneji, D., Rieger, K., Narala, S., Kim, Y. SAGE PUBLICATIONS LTD. 2023: 969

  View details for Web of Science ID 001091311306191

• Cutaneous larva migrans in the northeastern US. Dermatology online journal Johanis, M., Cheema, K. S., Young, P. A., Narala, S., Saleem, A., Novoa, R. A., Bae, G. H. 2023; 29 (4)

  Abstract

  Cutaneous larva migrans (CLM) is a dermo-epidermal parasitic infection with a disproportionate incidence in developing countries, particularly in, and near tropical areas. It is characterized by erythematous, twisting, and linear plaques that can migrate to adjacent skin. Herein, we present an otherwise healthy 45-year-old woman who acquired a pruritic, erythematous, and serpiginous rash localized to her right medial ankle during a trip to New England. Oral ivermectin, the preferred first-line treatment for cutaneous larva migrans, was administered in combination with triamcinolone. This was followed by removal of the papular area via punch biopsy; treatment was successful with a one-week recovery. Although cutaneous larva migrans has traditionally been considered a tropical disease, clinicians should be cognizant of its expanding geographic spread.

  View details for DOI 10.5070/D329461906

  View details for PubMedID 37921817

• Bullous impetigo on a young man's abdomen. Dermatology online journal Young, P. A., Leeolou, M. C., Narala, S., Saleem, A., Bae, G. H. 2023; 29 (1)

  Abstract

  Bullous impetigo is a variant of epidermal infection by Staphylococcus aureus, representing 30% of impetigo cases. Its clinical appearance may mimic certain autoimmune blistering dermatoses and other cutaneous infections, sometimes necessitating careful evaluation. Herein we present a patient with bullous impetigo in a striking and characteristic appearance and briefly overview the approach to diagnosis, treatment, and prevention.

  View details for DOI 10.5070/D329160220

  View details for PubMedID 37040917

• Progression of Mycosis Fungoides After Fingolimod Treatment for Multiple Sclerosis and Targeted Next-Generation Sequencing Demonstrating Potential Links Between the Two Diseases. JCO precision oncology Narala, S., Che, Y., Saleem, A., Lock, C. B., Kim, Y. H., Rieger, K. E. 2023; 7: e2200501

  View details for DOI 10.1200/PO.22.00501

  View details for PubMedID 36724412

• Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoproliferative disorder in a young woman. Dermatology online journal Leeolou, M. C., Young, P. A., Saleem, A., Narala, S., Bae, G. H. 2022; 28 (6)

  Abstract

  Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (CD4+PCSM-LPD) is a low-grade cutaneous T cell disorder. There is no standardized approach to treatment of CD4+ PCSM-LPD due to its rarity. Herein, we discuss a 33-year-old woman with CD4+PCSM-LPD which resolved after a partial biopsy. We highlight that conservative and local treatment modalities should be considered prior to utilizing more aggressive and invasive treatment options.

  View details for DOI 10.5070/D328659726

  View details for PubMedID 36809093

• Evanescent, episodic salmon-colored macules in a young woman. JAAD case reports Leeolou, M. C., Young, P. A., Dear, A. L., Narala, S., Saleem, A., Rieger, K. E., Bae, G. H. 2022; 29: 30-32

  View details for DOI 10.1016/j.jdcr.2022.08.022

  View details for PubMedID 36186409

• Burning urticarial plaques in a middle-aged woman. JAAD case reports Young, P. A., Saleem, A., Narala, S., Dear, A., Bae, G. H. 2022; 28: 138-141

  View details for DOI 10.1016/j.jdcr.2022.08.027

  View details for PubMedID 36164387

• Nontender white papule of the areola in a middle-aged female. JAAD case reports Young, P. A., Narala, S., Brown, R. A., Saleem, A., Rieger, K. E., Bae, G. H. 2022; 27: 6-8

  View details for DOI 10.1016/j.jdcr.2022.05.047

  View details for PubMedID 35941842

• Immunohistochemistry in melanocytic lesions: Updates with a practical review for pathologists. Seminars in diagnostic pathology Saleem, A., Narala, S., Raghavan, S. S. 1800

  Abstract

  This review provides a summary of the immunohistochemical markers pertinent to the diagnosis of melanocytic lesions. There is considerable morphologic overlap between benign and malignant melanocytic lesions, and given the significant differences in clinical management, the diagnostic workup becomes crucial. Immunohistochemistry aids in the distinction between various melanocytic proliferations and recent contributions to the literature have furthered our optimization of panels in the diagnostic workup. In recent years, SOX10 has been considered as the optimal marker for melanocytic lesions given the similar sensitivity but higher specificity than S100. HMB-45 is less sensitive than S100 but demonstrates utility in confirmation of deceptively banal small cell and nevoid melanoma variants where deep nests of melanocytes are highlighted. Melan-A (MART-1) and MiTF show similar sensitivity to S100 however there is a lack of expression in spindle cell and desmoplastic melanomas.

  View details for DOI 10.1053/j.semdp.2021.12.003

  View details for PubMedID 35016807

• Can quality keep up with quantity-Longitudinal trends in research output for the dermatology residency match. Clinics in dermatology Karri, P. V., Tahseen, D., Gupta, R., Grant-Kels, J. M., Narala, S., Patel, A. B. 2021; 39 (6): 1039-1045

  Abstract

  Dermatology is one of the most competitive specialties to match into and continually draws high-achieving medical students. According to National Residency Match Program data, applicants reported an increasing number of total research products throughout the past decade. To better contextualize this trajectory, our study investigates the specific types of research items underlying this trend and the impact of applicant-specific and program-specific factors on research output. Names of matched dermatology applicants from 2009, 2011, 2014, 2016, and 2018 were collected and searched on PubMed and Google Scholar to analyze research output. Applicants were further stratified by sex, PhD status, medical school attended, geography of matched program, domestic/international status, and whether they had a home dermatology program. Matched applicants reported a mean of 7.6 research products per applicant in 2018 and, of those products, had a mean of 2.55 peer-reviewed publications per applicant. This discrepancy was observed in other years. Matched applicants from the top 20 schools and applicants from men had a significantly higher mean of peer-reviewed publications. We observed that research volume did not impact an applicant's likelihood of matching to his/her home institution. The upward trend in total research products may be misleading, because applicants increasingly resort to nonindexed research (eg, abstracts, presentations, chapters) to be competitive for dermatology residency. We also observed preliminary evidence of certain applicant-specific factors (eg, attending a top 20 medical school, sex) correlating to increased applicant publications. There is a need for a more stringent and holistic method of evaluating applicant research.

  View details for DOI 10.1016/j.clindermatol.2021.07.007

  View details for PubMedID 34920822

• Application of least absolute shrinkage and selection operator logistic regression for the histopathological comparison of chondrodermatitis nodularis helicis and hyperplastic actinic keratosis. Journal of cutaneous pathology Narala, S., Li, S. Q., Klimas, N. K., Patel, A. B. 2021; 48 (6): 739-744

  Abstract

  The distinction between chondrodermatitis nodularis helicis (CNH) and hyperplastic actinic keratosis (HAK) on the ear can pose a diagnostic challenge. We aimed to identify histopathological characteristics that could distinguish between CNH and HAK on routine sections using penalized least absolute shrinkage and selection operator (LASSO) logistic regression analysis.Cases of CNH (n = 80) and HAK (n = 28) were analyzed for selected histopathological characteristics. Fisher's exact test and LASSO regression were performed.In univariate analyses, the following were significantly associated with CNH: ulceration, acanthosis, granular layer in the majority of the lesion, hypergranulosis at the periphery of the lesion, hyperkeratosis at the periphery of the lesion, hyperparakeratosis at the periphery of the lesion, fibrosis, increased blood vessels, vertically oriented blood vessels, and fibrin. A LASSO model excluding atypia found that fibrin, fibrosis, presence of granular layer, ulceration, and vertically oriented blood vessels were most predictive of CNH. Keratinized strap cells were not a significant predictor.We have identified features that may aid in differentiating these entities and demonstrated that a LASSO regression model can identify predictors that may improve diagnostic accuracy. Our results indicate that the highest diagnostic accuracy in this dilemma is dependent on obtaining biopsy specimens with visible dermis.

  View details for DOI 10.1111/cup.13931

  View details for PubMedID 33617003

• Alectinib-associated drug reaction with eosinophilia and systemic symptoms syndrome. JAAD case reports Farooq, S., Narala, S., Pacha, O. 2020; 6 (12): 1339-1341

  View details for DOI 10.1016/j.jdcr.2020.09.007

  View details for PubMedID 33304973

  View details for PubMedCentralID PMC7708757

• Palmoplantar eruption in a patient with mercury poisoning. Cutis McNally, M. A., Jenkinson, H., Narala, S., Rogge, M. 2020; 106 (5): 265-267

  Abstract

  Mercury poisoning is a rare event that can present with a variety of nonspecific systemic symptoms, making it difficult to diagnose. Dermatologic manifestations of mercury exposure may be variable and include pink disease (acrodynia), mercury exanthem, contact dermatitis, and cutaneous granulomas. We present the case of an 18-year-old woman with a palmoplantar eruption associated with tachycardia, hyperhidrosis, myalgia, paresthesia, and muscle fasciculations. Physical examination demonstrated poorly demarcated pink macules coalescing into patches on the left palm, right wrist, and soles. A punch biopsy was nonspecific, showing acanthosis and orthokeratosis with mild inflammation. Elevated urine and serum mercury levels confirmed a diagnosis of mercury poisoning. This case highlights the importance of consideration of mercury poisoning in the differential diagnosis for acral eruptions, especially in the presence of systemic symptoms and known risk factors.

  View details for DOI 10.12788/cutis.0113

  View details for PubMedID 33465192

• HIV patient with painless bilateral external ear nodules. JAAD case reports McNally, M., Narala, S., Koshelev, M. 2020; 6 (3): 222-224

  View details for DOI 10.1016/j.jdcr.2020.01.010

  View details for PubMedID 32123716

  View details for PubMedCentralID PMC7037540

• Characteristics of research tracks in dermatology residency programs: a national survey. Dermatology online journal Narala, S., Loh, T., Shinkai, K., Paravar, T. 2017; 23 (12)

  Abstract

  Pursuing research is encouraged in dermatology residency programs. Some programs offer specific research or investigative tracks. Currently, there is little data on the structure or scope of research tracks in dermatology residency programs. An anonymous online survey was distributed to the Association of Professors of Dermatology listserve in 2016. Program directors of dermatology residency programs in the United States were asked to participate and 38 of the 95 program directors responded. The survey results confirmed that a 2+2 research track, which is two years of clinical training followed by two years of research, was the most common investigator trackmodel and may promote an academic career at the resident's home institution. Further studies will help determine the most effective research track models to promote long-term outcomes.

  View details for PubMedID 29447650

• Adult Atopic Dermatitis with Comorbid Atopic Disease is Associated with Increased Risk of Infections: A Population-Based Cross-Sectional Study. Dermatology and therapy Narala, S., Hata, T. R. 2017; 7 (1): 111-121

  Abstract

  Atopic dermatitis (AD) is related to other atopic diseases asthma and allergic rhinitis. It is known that those with asthma or allergic rhinitis have impaired immune responses that may predispose them to infections. This study sought to determine whether adult AD is associated with systemic infections, and whether association is strengthened in those with AD plus another atopic disease.This cross-sectional study obtained information from adults in the 2010 and the 2012 National Health Interview Survey (NHIS). The primary exposure was history of AD without or with an additional atopic disease, asthma or allergic rhinitis. Self-reported systemic infections were the primary outcomes. Survey logistic regression was performed and adjusted odds ratios (aOR) reported.AD in NHIS 2010 was associated with increased risk of sinusitis [aOR (95% CIs): 1.65 (1.42, 1.91), P < 0.001], head or chest cold [1.31 (1.12, 1.52), P < 0.001], and gastrointestinal illness [2.39 (1.97, 2.89), P < 0.001], and in NHIS 2012, pneumonia/influenza [1.73 (1.54, 1.95), P < 0.001], strep throat/tonsillitis [1.72 (1.54, 1.92), P < 0.001], sinusitis [1.77 (1.54, 2.02), P < 0.001], head or chest cold [1.49 (1.33, 1.67), P < 0.001], and infectious disease [2.66 (2.20, 3.21), P < 0.001]. An increase in atopic disease mirrored an increase in number of infectious outcomes and was statistically significant in the combined dataset (P < 0.001).The associations between AD and AD plus another atopic disease with systemic infections suggest that an underlying immune defect may be contributing to microbial susceptibility. Further studies are warranted to understand the burden of infectious disease in this population.

  View details for DOI 10.1007/s13555-017-0172-7

  View details for PubMedID 28138890

  View details for PubMedCentralID PMC5336435

• Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Science translational medicine Nakatsuji, T., Chen, T. H., Narala, S., Chun, K. A., Two, A. M., Yun, T., Shafiq, F., Kotol, P. F., Bouslimani, A., Melnik, A. V., Latif, H., Kim, J. N., Lockhart, A., Artis, K., David, G., Taylor, P., Streib, J., Dorrestein, P. C., Grier, A., Gill, S. R., Zengler, K., Hata, T. R., Leung, D. Y., Gallo, R. L. 2017; 9 (378)

  Abstract

  The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing Staphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against S. aureus was performed on isolates of coagulase-negative Staphylococcus (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by S. aureus The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including Staphylococcus epidermidis and Staphylococcus hominis These AMPs were strain-specific, highly potent, selectively killed S. aureus, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S. aureus These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.

  View details for DOI 10.1126/scitranslmed.aah4680

  View details for PubMedID 28228596

  View details for PubMedCentralID PMC5600545

• Cutaneous T-cell lymphoma-associated Leser-Trélat sign: report and world literature review. Dermatology online journal Narala, S., Cohen, P. R. 2017; 23 (1)

  Abstract

  The sign of Leser-Trélat is characterizedby the sudden appearance of seborrheic keratosesassociated with an underlying malignancy.An elderly man who developed multiple new-onsetseborrheic keratoses temporally associated witha diagnosis of mycosis fungoides is described andlymphoma-associated Leser-Trélat sign is reviewed.Pubmed was used to search the followingterms: cutaneous T-cell lymphoma, Leser-Trélat,leukemia, lymphoma, mycosis fungoides, and Sézarysyndrome. Papers with these terms and referencescited within these papers were reviewed.An 84-year-old man developed multiple seborrheickeratoses temporally associated with a diagnosisof mycosis fungoides is presented. He was treatedwith bexarotene and achieved clinical remission;the number of seborrheic keratoses also decreased.Lymphoma-associated Leser-Trélat sign has beenobserved not only with mycosis fungoides but alsoother lymphomas and leukemias.Thesign of Leser-Trélat is predominantly associated withsolid organ adenocarcinomas. Albeit less common, aneruptive onset of seborrheic keratoses can also occurin association with hematopoietic malignancies.

  View details for PubMedID 28329468

• Staphylococcus aureus Exploits Epidermal Barrier Defects in Atopic Dermatitis to Trigger Cytokine Expression. The Journal of investigative dermatology Nakatsuji, T., Chen, T. H., Two, A. M., Chun, K. A., Narala, S., Geha, R. S., Hata, T. R., Gallo, R. L. 2016; 136 (11): 2192-2200

  Abstract

  Patients with atopic dermatitis (AD) have an abnormal skin barrier and are frequently colonized by S. aureus. In this study we investigated if S. aureus penetrates the epidermal barrier of subjects with AD and sought to understand the mechanism and functional significance of this entry. S. aureus was observed to be more abundant in the dermis of lesional skin from AD patients. Bacterial entry past the epidermis was observed in cultured human skin equivalents and in mice but was found to be increased in the skin of cathelicidin knockout and ovalbumin-sensitized filaggrin mutant mice. S. aureus penetration through the epidermis was dependent on bacterial viability and protease activity, because killed bacteria and a protease-null mutant strain of S. aureus were unable to penetrate. Entry of S. aureus directly correlated with increased expression of IL-4, IL-13, IL-22, thymic stromal lymphopoietin, and other cytokines associated with AD and with decreased expression of cathelicidin. These data illustrate how abnormalities of the epidermal barrier in AD can alter the balance of S. aureus entry into the dermis and provide an explanation for how such dermal dysbiosis results in increased inflammatory cytokines and exacerbation of disease.

  View details for DOI 10.1016/j.jid.2016.05.127

  View details for PubMedID 27381887

  View details for PubMedCentralID PMC5103312

• Basal Cell Carcinoma of the Umbilicus: A Comprehensive Literature Review. Cureus Narala, S., Cohen, P. R. 2016; 8 (9): e770

  Abstract

  Basal cell carcinoma (BCC) typically occurs in sun-exposed sites. Only 16 individuals with umbilical BCC have been described in the literature, and the characteristics of patients with umbilical BCC are summarized. PubMed was used to search the following terms: abdomen, basal cell carcinoma, basal cell nevus syndrome, and umbilicus. Papers with these terms and references cited within these papers were reviewed. BCC of the umbilicus has been reported in five men and 11 women; one man had two tumors. Two patients had basal cell nevus syndrome (BCNS). Other risk factors for BCC were absent. The tumor most commonly demonstrated nodular histology (64%, 9/14); superficial and fibroepithelioma of Pinkus variants were noted in three and two patients, respectively. The tumor was pigmented in eight individuals. Treatment was conventional surgical excision (87%, 13/15) or Mohs micrographic surgery (13%, 2/15); either adjuvant laser ablation or radiotherapy was performed in two patients. The prognosis after treatment was excellent with no recurrence or metastasis (100%, 16/16). In conclusion, BCC of the umbilicus is rare. It usually presents as a tumor with a non-aggressive histologic subtype in an individual with no risk factors for this malignancy. There has been no recurrence or metastasis following excision of the cancer.

  View details for DOI 10.7759/cureus.770

  View details for PubMedID 27738570

  View details for PubMedCentralID PMC5059144

• Establishment of an autologous microbiome transplant in atopic dermatitis targeting Staphylococcus aureus Nakatsuji, T., Narala, S., Chen, T. H., Chun, K. A., Hata, T., Gallo, R. L. ELSEVIER SCIENCE INC. 2016: S48

  View details for DOI 10.1016/j.jid.2016.02.303

  View details for Web of Science ID 000380028800273

• Noradrenergic neurons regulate monocyte trafficking and mortality during gram-negative peritonitis in mice. Journal of immunology (Baltimore, Md. : 1950) Seeley, E. J., Barry, S. S., Narala, S., Matthay, M. A., Wolters, P. J. 2013; 190 (9): 4717-24

  Abstract

  Effective host defense requires a robust, yet self-limited response to pathogens. A poorly calibrated response can lead to either bacterial dissemination due to insufficient inflammation or organ injury due to excessive inflammation. Recent evidence suggests that the cholinergic anti-inflammatory reflex helps calibrate the immune response. However, the influence of peripheral noradrenergic neurons, which are primarily sympathetic neurons, in regulating immunity remains incompletely characterized. Using a model of 6-hydroxydopamine-mediated noradrenergic nerve ablation, we show that elimination of noradrenergic neurons improves survival during Klebsiella pneumoniae peritonitis (67 versus 23%, p < 0.005) in mice. The survival benefit results from enhanced MCP-1-dependent monocyte recruitment and a subsequent decrease in bacterial loads. Splenectomy eliminated both the survival benefit of 6-hydroxydopamine and monocyte recruitment, suggesting that monocytes recruited to the peritoneum originate in the spleen. These results suggest that noradrenergic neurons regulate the immune response through two pathways. First, sympathetic nerve-derived norepinephrine directly restrains MCP-1 production by peritoneal macrophages during infection. Second, norepinephrine derived from the vagally innervated splenic nerve regulates splenic monocyte egress. Removal of these two modulators of the immune response enhances antibacterial immunity and improves survival. These results may have implications for how states of catecholamine excess influence the host response to bacterial infections.

  View details for DOI 10.4049/jimmunol.1300027

  View details for PubMedID 23543756

  View details for PubMedCentralID PMC3973442

• Primary Hyperoxaluria in Cats Is Caused by a Mutation in the Feline GRHPR Gene Goldstein, R. E., Narala, S., Sabet, N., Goldstein, O., McDonough, S. P. OXFORD UNIV PRESS INC. 2009: S2-S7

  View details for DOI 10.1093/jhered/esp038

  View details for Web of Science ID 000268578400002