Letters

1. Picardi A, Pasquini P, Cattaruzza MS, et al. Psychosomatic factors in first- Another prevalent transverse linear crease of the face, the onset alopecia areata. Psychosomatics. 2003;44(5):374-381. nasal crease, appears across the lower third of the nasal dor- 2. Vannatta K, Gartstein MA, Zeller MH, Noll RB. Peer acceptance and social sum. In some cases, changes of pigmentation, milia, or pseudo- behavior during childhood and adolescence: how important are appearance, comedones are present along the nasal crease.5 Transverse na- athleticism, and academic competence? Int J Behav Dev. 2009;33(4): 303-311. sal milia in the absence of a transverse nasal crease are less frequently reported. Recently, our research team6 reported a OBSERVATION case of seborrheic keratosis–like hyperplasia and horn cysts aligned along this crease. These findings were attributed to the Deep Labiomental Fold With Pseudocomedones fact that the triangular cartilage and the alar cartilage attach The labiomental fold is a transverse indentation of the face, in a linear fashion at the junction of the middle and lower third which marks the intersection of the lower lip and chin.1 It plays of the nose, producing a potential embryonic fault line in which a significant role in movement of the lower lip and in facial ex- retention cysts presenting as milia and comedones can occur.5 pression. We describe herein a child with a linear pattern of Early acne lesions favor the forehead, nose, and chin in microcomedones located along a deep labiomental fold. many children. Although many times overlooked, the exter- nal ear is another common location for open and closed com- Report of a Case | A 7-year-old healthy girl presented with a line edones in young patients with acne.7 We think that the com- of black papules on her chin. On examination, the child had a mon concave surface of the nasal crease, deep labiomental fold, protruded chin with a relatively deep labiomental groove. Sev- and external ear may facilitate the appearance of retention le- eral open comedones were aligned along the groove (Figure). sions in those locations. Acneiform lesions were not present in any other location on In conclusion, we think that the labiomental fold, a trans- her face or upper trunk. verse fold of the chin, can harbor retention cysts or comedo- nes in a similar fashion to the nasal crease. Dermatologists Discussion | Three muscles, the circular orbicularis oris, depres- should be aware of this fold, since it might be encountered in sor labii inferioris, and mentalis align the labiomental fold or the dermatology practice and may be associated with addi- cross it as they pass to their insertion.2 The fibers of the 3 tional dermatologic conditions. muscles are attached to the skin by thick bands of fibroelastic fibers. The mentalis muscles originate from the mandible and Liran Horev, MD serve as paired elevators of the central lower lip.3 They usu- Abraham Zlotogorski, MD ally overlap and insert into the deep dermis of the chin pad. Yuval Ramot, MD, MSc Patients with substantial overlap of the mentalis muscles tend to have a deep labiomental fold.3 The presence of a deep la- Author Affiliations: Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel (Horev, Zlotogorski, Ramot). biomental fold is a relatively common condition and may some- Corresponding Author: Liran Horev, MD, Department of Dermatology, times cause an aesthetic concern.4 Procedures for treating deep Hadassah-Hebrew University Medical Center, PO Box 12000, Jerusalem 91120, labiomental fold are sometimes discussed in the plastic sur- Israel ([email protected]). gery literature, but it has been rarely reported in the derma- Conflict of Interest Disclosures: None reported. tology literature. To our knowledge, this is the first report of a 1. Reyneke JP, Ferretti C. Clinical assessment of the face. Semin Orthod. dermatologically related condition associated with this fold. 2012;18(3):172-186. 2. Cardoso ER, Amonoo-Kuofi HS, Hawary MB. Mentolabial sulcus: a histologic study. Int J Oral Maxillofac Surg. 1995;24(2):145-147. Figure. Deep Labiomental Fold and Open Comedones in a Linear Pattern 3. Garfein ES, Zide BM. Chin ptosis: classification, anatomy, and correction. Along the Fold Craniomaxillofac Trauma Reconstr. 2008;1(1):1-14. 4. Suryadevara AC. Update on perioral cosmetic enhancement. Curr Opin Otolaryngol Head Neck Surg. 2008;16(4):347-351. 5. Waller B, Haber RM. Transverse nasal crease and transverse nasal milia: clinical variants of the same entity. Arch Dermatol. 2012;148(9):1037-1039. 6. Ramot Y, Maly A, Zlotogorski A, Nanova K. Atypical “allergic crease”. J Dermatol Case Rep. 2010;4(3):36-37. 7. del Río E. Peculiar distribution of comedones: a report of three cases. Dermatology. 1997;195(2):162-163.

Successful Treatment of Ulcerative and Diabeticorum Necrobiosis Lipoidica With Intravenous Immunoglobulin in a Patient With Common Variable Immunodeficiency Necrobiosis lipoidica (NL) is an idiopathic inflammatory skin disorder that rarely resolves spontaneously, and ulceration is a major complication. Although NL occurs in less than 1% of patients with diabetes mellitus, 75% of NL cases are associ- Several comedone openings are marked by arrows. ated with diabetes.1

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Figure 1. Clinical Images of Affected Areas Before Treatment

A B

Lower pretibial right (A) and left (B) legs before intravenous immunoglobulin therapy showing large and ulcerative plaques of necrobiosis lipoidica.

Common variable immunodeficiency (CVID) is the most Figure 2. Clinical Image of Affected Areas After Treatment frequent symptomatic primary immunodeficiency encoun- tered in adults: incidence is estimated at between 1 in 10 000 and 1 in 50 000. Because of the heterogeneity of this disor- der, no targeted therapy has been defined except intravenous immunoglobulin (IVIG).2 Herein, we describe a patient with diabetes who experienced a successful combined treatment of NL ulcers and CVID with IVIG.

Report of a Case | A 63-year-old white woman with diabetes was referred to us with a 7-year history of ulcerating and very painful NL lesions on her shins, which had gradually enlarged during this period. The patient was a smoker and had a history of well-controlled type 2 insulin-treated diabe-

tes mellitus (hemoglobin A1c proportion, 6.1%) with no addi- tional diabetic complication. Physical examination revealed atrophic, yellow-brown, telangiectatic plaques affecting her lower legs. The lesions had large, deep, and crusting ulcer- ations (Figure 1). Cutaneous biopsy findings were compat- ible with NL, and direct immunofluorescence findings were negative. The patient had previously received treatments with topical corticosteroid, topical tacrolimus, hydroxychlo- roquine, psoralen plus UV-A, and pentoxifylline without any significant clinical response. Owing to recurring ear, nose, and throat infections, CVID was suspected. Immunologic tests revealed a poor response to vaccines (pneumococcus and diphtheria) and reduced serum immunoglobulin con- centrations (IgG, IgM, and IgA at 77, 23, and 40 mg/dL, respectively). No secondary cause of hypogammaglobu- linemia was observed (no history of immunosuppressive therapy, digestive symptoms of inflammatory disease, nor Lower pretibial aspect of the legs after Intravenous Immunoglobulin therapy evidence for neoplasia by thoraco-abdominal computed showing substantial healing. tomographic scan and flow cytometry).

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The patient was subsequently treated with IVIG, 0.4g/ Intralesional Cidofovir for Treating Extensive Genital kg/d, for 5 consecutive days for her newly diagnosed CVID, Verrucous Herpes Simplex Virus Infection while local application of paraffin gauze dressing (Jelonet; Verrucous herpes simplex viral infections in immunocom- Smith & Nephew) was maintained. Surprisingly, 3 weeks promised patients can be a therapeutic challenge, and we after this single cycle, all ulcerations had healed (Figure 2), present a case of successful treatment with intralesional and complete resolution of pain was reported. The immu- cidofovir. noglobulin levels remained stable 3 months after IVIG treat- ment, and no further ulcerations were detected during a Report of a Case | A 55-year-old man with human immunodefi- 2-year follow-up, and so the patient did not require addi- ciency virus (HIV) and hepatitis C virus coinfection pre- tional therapy. sented with new lesions on his scrotum and perianal area. He noted mild tingling and slow growth over the prior 2 months. Discussion | In our case, no significant success was observed in His medications included darunavir, ritonavir, emtricitabine/ reduction of NL ulcers after administration of currently ac- tenofovir, and trimethoprim-sulfamethoxazole. His CD4 count cepted treatments, the efficiency of which was known to be was stable at 350 cells/μL, and he had an undetectable HIV vi- limited. Interestingly, treatment of the patient’s CVID with IVIG ral load. Findings of a comprehensive metabolic panel and com- appeared to heal the ulcers within 3 weeks. As the IVIG treat- plete blood cell count were normal, and rapid plasma reagin ment showed a similar dramatic ulcer reduction within 2 weeks was nonreactive. Physical examination was notable for exo- inapreviouscase3 (where no investigation of associated hy- phytic, verrucous, and ulcerated plaques on his right inferior pogammaglobulinemia was performed), the immunologic as- scrotum and perianal area (Figure 1A and B). Biopsy and tis- pect of NL appears of major importance in these patients. Be- sue culture were performed. Histopathologic analysis dem- cause of its strong association with diabetes, NL has been onstrated full-thickness epidermal ulceration with adjacent postulated to arise due to microangiopathic vascular changes. pseudoepitheliomatous hyperplasia (Figure 2A and B). Mul- Therefore, NL might be due to immunologically mediated vas- tinucleated keratinocytes with peripheral rimming of nuclear cular changes.4,5 In this context, measures of serum immu- chromatin were present at the edge of the ulceration (Figure 2B noglobulin levels and direct immunofluorescent histologic and C), and immunostaining for herpes simplex virus (HSV) study might be recommended in NL. was positive, confirming HSV infection (Figure 2D). Gram and Our findings suggest that IVIG can be a successful option periodic acid-Schiff stainings and Treponema pallidum im- in the treatment of NL, particularly in patients with CVID, while munostaining were negative. Tissue culture had no growth, a broader approach in NL without underlying CVID requires and viral resistance testing could not be performed. further investigations. The patient began treatment for HSV, and despite suc- cessive 1-month courses of high-dose oral acyclovir, valacy- Neda Barouti, MD clovir, and famciclovir, his lesions progressed. A repeated Amy Qian Cao, H BSc tissue culture for viral resistance testing was not successful Donato Ferrara, MD in growing virus. A repeated biopsy confirmed the original Christa Prins, MD diagnosis of verrucous HSV. Given concern for acyclovir- resistant HSV, oral therapy was discontinued, and intrave- nous (IV) cidofovir treatment was initiated, with improve- Author Affiliations: Department of Medical Specialties–Dermatology, ment noted after 3 doses. This treatment was complicated by University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland (Barouti, Qian Cao, Ferrara, Prins); Queen’s University School of Medicine, elevations in serum creatinine levels and discontinued. Kingston, Ontario, Canada (Qian Cao). Intralesional cidofovir was then initiated every other week, 1 Corresponding Author: Neda Barouti, MD, Rue Gabrielle-Perret-Gentil 4, 1205 as previously reported, with resolution of his scrotal lesion Genève, Switzerland ([email protected]). and dramatic improvement in his perianal lesion after 6 Conflict of Interests Disclosures: None reported. treatments (Figure 1C and D). Funding/Support: This study was supported by the University Hospitals of Geneva, Geneva, Switzerland. Discussion | Herpes simplex virus infections cause significant Role of the Sponsors: The sponsors had no role in the design and conduct of morbidity in immunocompromised patients, and active HSV the study; in the collection, analysis, and interpretation of data; or in the infection increases HIV transmission.2 Infection with acyclovir- preparation, review, or approval of the manuscript. resistant HSV strains is about 10-fold higher in patients with 1. Ngo B, Wigington G, Hayes K, et al. Skin blood flow in necrobiosis lipoidica diabeticorum. Int J Dermatol. 2008;47(4):354-358. HIV than in immunocompetent individuals and appears re- 2. Salzer U, Warnatz K, Peter HH. Common variable immunodeficiency: an lated to the degree of immunosuppression and duration of an- update. Arthritis Res Ther. 2012;14(5):223. tiretroviral therapy.2 Treatment options for acyclovir- 3. Batchelor JM, Todd PM. Treatment of ulcerated necrobiosis lipoidica with resistant HSV are limited and include foscarnet, cidofovir, intravenous immunoglobulin and methylprednisolone. J Drugs Dermatol. imiquimod, and immunomodulating dipeptides.3,4 Foscar- 2012;11(2):256-259. net and cidofovir are not dependent on phosphorylation of vi- 4. Quimby SR, Muller SA, Schroeter AL. The cutaneous immunopathology of ral thymidine kinase for activation and can therefore be used necrobiosis lipoidica diabeticorum. Arch Dermatol. 1988;124(9):1364-1371. in acyclovir-resistant cases; however, both have limited for- 5. Laukkanen A, Fräki JE, Väätäinen N, Korhonen T, Naukkarinen A. Necrobiosis lipoidica: clinical and immunofluorescent study. Dermatologica. 1986;172(2): mulations, and drug-induced nephrotoxic effects are poten- 89-92. tially serious complications. Topical and intralesional admin-

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