Faculty Bibliography

Background/Purpose: Based on inhibition of viral replication and limited reports on clinical efficacy, hydroxychloroquine (HCQ) was initially considered as a prophylaxis and treatment of COVID-19. Despite this optimism, more extensive reports have significantly dampened the promise of efficacy, however cardiac toxicity has surfaced raising attention to this complication. Although HCQ is generally considered safe during pregnancy based on studies in patients with systemic lupus erythematous and other rheumatic conditions, this initiative leveraged a unique opportunity to evaluate neonatal electrocardiograms (ECGs) in the context of HCQ levels to address any potential cardiotoxicity.
Method(s): Neonatal ECGs and HCQ blood levels were available in a recently completed study evaluating the efficacy of HCQ 400mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro antibodies. The ECGs of affected newborns who met the primary outcome of advanced block were not included in this safety study so that the results only reflect those infants with no clinical cardiac disease. Using the Bazett formula to correct for heart rate, corrected QT (QTc) intervals were calculated and compared to age-matched normal values. For reference, the median (2nd percentile - 98th percentile) values for QTc were 413 (378-448) msec in males, and 420 (379-462) msec in females. QTc intervals were recorded in the absence of knowledge of the HCQ levels. Values exceeding 448 msec for males and 462 msec for females were considered abnormal. Levels of HCQ were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure.
Result(s): There were 45 ECGs available for interpretation within the first 4 months of life in unaffected infants. Overall, there was no correlation between cord blood levels of HCQ and the QTc (R = 0.02, P = 0.86) or the average value of HCQ levels obtained during each individual pregnancy and cord blood and the QTc (R = 0.04, P = 0.80), as shown in Figure 1A and Figure 1B. Likewise there was no correlation between the average of the maternal HCQ levels obtained at each trimester and delivery plus cord levels and the QTc on the ECGs of the 31 infants evaluated on day of life 1-4 (R = 0.08, P = 0.63) or those of the 14 children older than 4 days (R = 0.01, P = 0.95). Maternal values of HCQ were sustained throughout pregnancy and delivery (Figure 2). Mean QTc values were nearly identical between those in the highest and lowest quartiles of cord blood HCQ levels (P = 0.57) and between the highest and lowest quartiles of average HCQ levels during pregnancy (P = 0.54) (Figure 3A and 3B). Among these 45 infants, only 5 had prolongation of the QTc (11%; 95% CI: 4% - 24%), 2 marked and 3 marginal. No arrhythmias occurred in any neonate that was not known to have heart block.
Conclusion(s): In aggregate, these data provide reassurances that the maternal use of HCQ is not associated with a high incidence of QTc prolongation in the neonate

Background/Purpose : Pregnancy counseling of all anti-Ro positive women includes advice regarding the development of congenital heart block (CHB), albeit the risk is only 2% for primigravida women or those with previously unaffected offspring. Despite this low risk, the prevailing surveillance recommendation is weekly echocardiography. While evidence from basic research laboratories support that high titers of antibodies confer clinically meaningful risk, unfortunately the majority of commercial laboratories use the BioPlex assay, which provides positive and negative values with limited information on actual levels because the sera or plasma are not diluted past a specified cutoffgiven cost (e.g. values of anti-Ro inclusive of Ro52 or Ro60 by laboratories such as Quest or LabCorp provide positive as 1-8 or > 8 units with no further information). The present study was initiated to assess whether the Bio-Plex assay used by many commercial laboratories provides adequate stratification of risk for counseling regarding management. Methods : The study group comprised healthy non-pregnant donors (N = 9), healthy pregnant donors (N = 62), women testing positive for anti-Ro by commercial BioPlex but without CHB children (N = 60 SLE and 2 SS), and women with CHB children (N = 83). Anti-Ro60 reactivity was assessed using native antigen and anti-Ro52 using recombinant protein. Sera were applied to coated microtiter plates at serial dilutions ranging from 1:1000 -1:50,000 for 1h at RT and run in duplicate. Tested samples were multiplied by the dilution factor which gives an OD in the range of 0.3-0.8. Results were considered positive at 123 ELISA units (EU) for Ro60 and 215 EU for Ro52 as this represented the mean +3 SD of the values obtained for healthy control sera. Results : Of the 83 CHB mothers tested, 74 had titers of Ro60 and Ro52 > 1000 EU, in 1 anti-Ro60 was > 1000 EU and anti-52 Ro between 215 -1000, in 3 anti-Ro52 was > 1000 EU and anti-Ro60 between 300 -1000, and 1 mother had anti-Ro60 > 1000 EU and was negative for anti-Ro52. Albeit all positive, the sera from 4 CHB mothers obtained 15 years after the birth of the affected child were < 1000 EU for both anti-Ro60 and Ro52. With these results setting thresholds ( > 1000 EU in either Ro60 or Ro52 for CHB risk), we assessed patients testing positive for anti-Ro based on the BioPlex assay. Of 42 patients with values of > 8 on BioPlex testing, 14 had titers > 1000 EU for both anti-Ro60 and Ro52, 7 had anti-Ro60 > 1000 EU, and 8 had anti-Ro52 > 1000 EU. Thus, 13 of 42 (25%) with commercial Ro > 8 did not meet the threshold EU for CHB risk. Of 20 patients considered positive for anti-Ro by BioPlex with values between 1-8, none had levels of either anti-Ro60 or Ro52 at 1000 EU. No patient or healthy control testing negative by the BioPlex assay was positive for CHB risk in our ELISA. Conclusion : These data suggest that commercial testing using the BioPlex assay may fall short of stratifying risk for CHB. Women with positive values < 8 are not likely at risk, obviating the cost and burden of weekly fetal echo surveillance. Moreover, even those considered high titer on commercial testing may be at low risk supporting the need for more quantitative commercial testing than is currently available. (Figure Presented)

Both patients and medical professionals are increasingly accessing the Internet for health information. Today's Web enables features that facilitate information sharing in a social and collaborative manner, thus transforming the way we access data and communicate with our patients and colleagues. The visual nature of the field of dermatology lends itself to the use of the Internet for reference and educational purposes. To generate a list of Web sites commonly used by academic dermatologists, the authors polled the Accreditation Council for Graduate Medical Education Dermatology Program Directors for their top 3 Web resources. The purpose of this article is to identify resources used by dermatologists as well as patients and examine factors that can influence Internet search results. Concerns regarding professionalism in the era of social media are also explored. As the volume of health information on the Internet continues to increase, it is essential for physicians to be aware of what is available in cyberspace. Reference and learning tools for the physician, learning and support tools for the patient, and physician Internet presence are key aspects of modern dermatology practice.

A 57-year-old man presented with the post-pubertal onset of asymptomatic swelling of the left arm and legs that had been complicated by recurrent bouts of cellulitis. The presentation and disease course are consistent with lymphedema praecox, which is a subtype of primary lymphedema with onset at puberty and a slowly progressive course. The subtypes of lymphedema, pathogenesis, and treatment are reviewed.

A 64-year-old man presented with a superficial, well-demarcated, skin-colored tumor on the left posterior scalp that measured 4 x 5 x 6 cm. The tumor was nearly hairless, rubbery, non-tender, and mobile over the underlying subcutaneous tissues. The lesion had grown slowly since arising approximately 30 years ago. Treatment options were declined in the past. However, with relatively more rapid growth over the past five years, the nodule began to cause intermittent pain and interfere with the patient's ability to lie on his back. The patient denied a history of similar lesions in himself or his family. A biopsy specimen showed a ruptured proliferating trichilemmal cyst with focal calcification. Complete excision is recommended for all benign proliferating variants owing to their potential for locally aggressive behavior and malignant transformation

BACKGROUND: Melanoma is completely curable if resected early. Unfortunately, early melanoma can be difficult to differentiate from other pigmented lesions. Computerized image analysis instruments have now been developed to assist in determining whether a pigmented lesion is potentially dangerous and requires biopsy. To evaluate whether one such instrument can improve the management of pigmented lesions, we obtained biopsy specimens from 52 pigmented lesions that appeared clinically benign to an experienced dermatologist but were suspicious by image analysis. OBSERVATION: Histologically, 9 (17%) of the lesions that were removed based solely on computer recommendation were potentially dangerous and should have been removed. These included 1 malignant melanoma in situ and 8 dysplastic nevi with moderate to severe cytologic atypia. CONCLUSION: The results of the present study indicate that computerized image analysis can improve the evaluation of pigmented skin lesions by identifying clinically unsuspicious, but potentially dangerous, lesions that might have otherwise have been neglected