Cutaneous Neonatal Lupus Arising in an Infant Conceived from An

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Cutaneous Neonatal Lupus Arising in an Infant Figure 1. Cutaneous Neonatal Lupus Conceived From an Oocyte Donation Pregnancy As the pathogenesis behind neonatal lupus erythematosus (NLE) is thought to require both gestational factors, such as circulating maternal autoantibodies, and an underlying fetal genetic susceptibility,1 we report an informative case of cutaneous NLE involving an infant conceived through in vitro fertilization with a healthy oocyte donor and a gestational mother with Sjögren syndrome (SS), demonstrating that direct inheritance of genetic susceptibility from a mother af- flicted with autoimmunity is not required for NLE.

Report of a Case |A 4-week-old otherwise healthy,full-term Asian American female infant presented with a 10-day history of annular, erythematous scaling plaques of the forehead and bi- lateral preauricular and postauricular regions (Figure 1). No- tably, she was conceived via an unrelated donor oocyte and paternal sperm. Her gestational mother, who carried the patient to term, had a 10-year history of SS and was known to have tested positive for anti-Ro/SSA and anti-La/SSB antibodies. The father and the oocyte donor both reported no known history of autoimmune disease or other major medical problems. Given her gestational mother’s history of SS, the patient underwent an in utero fetal echocardiogram at 32 weeks’ gestation, and Clinical photograph of patient demonstrating characteristic annular, the results were normal. All other fetal ultrasonograms and an scaling plaque. electrocardiogram obtained at birth were unremarkable. A punch biopsy of a facial lesion from the infant demon- Figure 2. Punch Biopsy Specimen From a Facial Lesion strated vacuolar interface changes overlying a dense lympho- histiocytic infiltrate also containing numerous neutrophils (Figure 2). Numerous CD123-positive dendritic cells were also present within the infiltrate. Laboratory findings were positive for anti-Ro/SSA IgG and anti-La/SSB IgG; her antinuclear antibody titer was 1:80 with a coarse speckled pattern; and she demonstrated a mild transaminitis (aspartate transaminase [AST], 109 IU/L; alanine transaminase [ALT], 158 IU/L. Find- ings for the anti-U1RNP, anti-Smith, and anti–Jo-1 antibodies were negative. Findings of a repeat electrocardiogram, complete blood cell count, and thyroid studies were normal. As she continued to develop new lesions on the face and upper trunk over the next month, the patient was started on a treatment regimen of desonide, 0.05%, ointment for the face and triam- cinolone, 0.1%, ointment for the trunk. Recommendations were provided regarding strict sun avoidance. At age 8 weeks, the patient’s liver function test results A punch biopsy performed on a scaling plaque on the patient’s face at age 4 weeks reveals a vacuolar interface dermatitis overlying a dense dermal infiltrate peaked (AST, 518 IU/L; ALT, 648 IU/L; and alkaline phospha- composed of neutrophils, lymphocytes, and histiocytes, supporting the tase, 412 IU/L). These values subsequently down-trended and diagnosis of neonatal lupus (hematoxylin-eosin, original magnification ×200). normalized by age 5 months. Skin examination at that time re- vealed only postinflammatory hyperpigmentation. By age 1 year, her skin lesions had resolved without scarring. been difficult to assess the relative contributions of these factors because in nearly all cases, the infant is related to the af- Discussion | We describe the first case to our knowledge of cu- fected mother. Our case involving the unique situation of NLE taneous manifestations of NLE developing in an infant con- arising from an in vitro fertilization pregnancy suggests that ceived from a healthy oocyte donor and born to a gestational while fetal genetic susceptibility may be required, direct trans- mother with a history of autoimmune disease with circulat- mission of these genes from the gestational mother is not. ing anti-Ro and anti-La antibodies. The pathogenesis of NLE We note a supportive report in the rheumatology litera- is thought to involve a complex interplay between maternal ture describing an infant who developed heart block after birth factors such as circulating autoantibodies, the in utero envi- to a surrogate mother with circulating anti-Ro/SSA antibod- ronment, and underlying fetal genetic susceptibility.1-3 It has ies, likely representing cardiac-predominant NLE.4 This case,

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in combination with the present patient’s classic cutaneous pre- nail disorder, it may present similarly to benign nail dis- sentation, would indicate that the full spectrum of NLE’s mani- eases, including lichen planus, psoriasis, verruca, bacterial festations can occur in the absence of autoimmunity in the ma- infections, subungual exostosis, and onychomatricoma,2 ternal genetic donor. Therefore, from a clinical perspective, we each requiring vastly different treatments. An erroneous suggest that NLE should be considered possible in an infant diagnosis would be even more detrimental with malignant when there is a history of autoimmune connective tissue dis- nail conditions, such as squamous cell carcinoma and ease or appropriate circulating IgG autoantibodies in the ges- melanoma.2 Furthermore, while highly trained dermatolo- tational mother. gists and podiatrists may be able to make the diagnosis of onychomycosis clinically in many cases, general practition- Albert Sean Chiou, MD ers and physician extenders would have less diagnostic pre- Grace Sun, MD cision. All things considered, treatment for presumed ony- Jinah Kim, MD, PhD chomycosis without laboratory confirmation may cause Kevin Chun-Kai Wang, MD, PhD misdiagnosis, serious complications,3 and medicolegal Ann L. Marqueling, MD costs. Mikailov et al1 properly base their cost calculation on the Author Affiliations: Department of Dermatology, Stanford University School of incidence of clinically apparent liver injury due to terbin- Medicine, Palo Alto, California (Chiou, Kim, Wang, Marqueling); Dermatology afine. However, additional clinically significant adverse Medical Group of Oxnard and Camarillo, Camarillo, California (Sun). effects of terbinafine, including severe neutropenia and Corresponding Author: Ann L. Marqueling, MD, Department of Dermatology, 4 Stanford University School of Medicine, 770 Welch Rd, Ste 261, Palo Alto, CA toxic epidermal necrolysis, should also be included. To be 94304 ([email protected]). complete, the other oral treatment option approved by the Published Online: March 9, 2016. doi:10.1001/jamadermatol.2016.0001. US Food and Drug Administration, itraconazole, with poten- Additional Contributions: We thank the patient’s parents for granting tial adverse effects such as liver failure, peripheral neuropa- permission to publish this information. We also thank Mary Le, MD, for helpful thy and cardiovascular events,5 should be analyzed. Both of discussion. Dr Le was not compensated for her contributions. these oral medications may also interact with the patients’ 1. Chang C. The pathogenesis of neonatal autoimmune and autoinflammatory existing drugs through the CYP450 system, causing other diseases: a comprehensive review. J Autoimmun. 2013;41:100-110. adverse effects. 2. Buyon JP, Clancy RM. Neonatal lupus: review of proposed pathogenesis and 1 clinical data from the US-based Research Registry for Neonatal Lupus. While Mikailov et al have written an important cost Autoimmunity. 2003;36(1):41-50. analysis on laboratory confirmation prior to treatment 3. Batard ML, Sainte-Marie D, Clity E, Belhabri S, Cotellon P, Pradinaud R. for onychomycosis, as dermatologists we have an obligation Cutaneous neonatal lupus erythematosus: discordant expression in identical to weigh other factors, such as patient morbidity and mor- twins [in French]. Ann Dermatol Venereol. 2000;127(10):814-817. tality. We strongly advocate that physicians confirm the 4. Brucato A, Ramoni V, Penco S, Sala E, Buyon J, Clancy R. Passively acquired diagnosis before initiating treatment in all cases of nail anti-SSA/Ro antibodies are required for congenital heart block following 3 ovodonation but maternal genes are not. Arthritis Rheum. 2010;62(10):3119-3121. dystrophy.

Shari R. Lipner, MD, PhD COMMENT & RESPONSE Richard K. Scher, MD

Confirmatory Testing for Onychomycosis Author Affiliations: Department of Dermatology, Weill Cornell Medicine, New To the Editor We read with great interest the article by Mikai- York, New York. lovetal1 on the cost-effectiveness of laboratory testing be- Corresponding Author: Shari R. Lipner, MD, PhD, Department of Dermatology, fore treatment of onychomycosis. In this article, the authors Weill Cornell Medicine, 1305 York Ave, New York, NY 10021 (shl9032@med .cornell.edu). did a substantial analysis of the cost and potential harm Conflict of Interest Disclosures: Dr Lipner has served on the advisory board for associated with 3 methods of onychomycosis assessment Sandoz. Dr Scher has been a consultant for several pharmaceutical companies prior to therapy with oral terbinafine or efinaconazole, 10%. including Valeant. No other disclosures are reported. They include the potassium hydroxide and periodic acid– 1. Mikailov A, Cohen J, Joyce C, Mostaghimi A. Cost-effectiveness of Schiff stainings, which are commonly performed in derma- confirmatory testing before treatment of onychomycosis. JAMA Dermatol. tological practices. Fungal culturing should be included 2016;152(3):276-281. because it is the only test that can prove the viability and 2. Lipner SR, Scher RK. Onychomycosis: diagnosis and therapy. In: Razzaghi-Abyaneh M, Shams-Ghahfarokhi M, Rai M, eds. Medical Mycology: identity of the organism. It is particularly important when Current Trends and Future Prospects. Boca Raton, FL: CRC Press; 2015. nondermatophytes or yeast are suspected, which may not 3. Lipner SR, Scher RK. Onychomycosis: a small step for quality of care. Curr respond to terbinafine. Med Res Opin. 2016;32(5):865-867. The authors stress that traditionally, confirmatory test- 4. Lamisil. Package Insert: LAMISIL (terbinafine hydrochloride) Tablets, 250 mg ing before treating onychomycosis was largely driven by Drugs@FDA: FDA Approved Drug Products 2012 [21 June 2014]. http://www drug costs. However, there are more compelling reasons to .accessdata.fda.gov/drugsatfda_docs/label/2012/020539s021lbl.pdf. Accessed January 14, 2016. perform this testing that are not based on economics alone. Empirical treatment of nail dystrophy that is assumed to be 5. Sporanox. Package insert: SPORANOX! (itraconazole) Capsules. Drugs@FDA: FDA Approved Drug Products 2012 [21 June 2014]. http://www.accessdata.fda onychomycosis may result in treatment failures and incor- .gov/drugsatfda_docs/label/2012/020083s048s049s050lbl.pdf. Accessed rect diagnoses. While onychomycosis is the most common January 14, 2016.

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