Lip Angioedema Swellimng and HSV Following HA Inj

J AM ACAD DERMATOL Letters e21
VOLUME 65, NUMBER 1
histopathologic findings and localization of orga-

nisms in this case proves once again that syphilis
continues to be ‘‘The Great Mimicker.’’
Adrienne C. Jordan, MD,a Stephen E. Mercer, MD,
PhD,a Barry D. Goldman, MD,b and Patrick O.
Emanuel, MBChBa,c
Division of Dermatopathology, Mount Sinai School
of Medicine,a Department of Dermatology, New
York Downtown Hospital,b New York, New York,
and Diagnostic Medlab, Auckland, New Zealandc
Funding sources: None.
Fig 1. Angioedema-type swelling 12 hours after injection
Conflicts of interest: None declared. of hyaluronic acid (Restylane-Medicis Aesthetics) into
lips.
Reprints requests: Patrick O. Emanuel, MBChB,
Diagnostic Medlab, 10 Harrison Road, Mount
Wellington, Auckland, New Zealand.
E-mail: [email protected]
REFERENCES
1. Quatresooz P, Pierard GE. Skin homing of Treponema pallidum
in early syphilis: an immunohistochemical study. Appl Immu-
nohistochem Mol Morphol 2009;17:47-50.
2. Phelps RG, Knispel J, Tu ES, Cernainu G, Saruk M. Immunoperox-
idase technique for detecting spirochetes in tissue sections:
comparison with other methods. Int J Dermatol 2000;39:
609-13.
3. Jeerapaet P, Ackerman AB. Histologic patterns of secondary
syphilis. Arch Dermatol 1973;107:373-7.
Fig 2. Monomorphous vesicles and crusted papules with
4. Buffet M, Grange PA, Gerhardt P, Carlotti A, Calvez V, Bianchi A,
collarettes of scale localized to vermilion border of lips 3
et al. Diagnosing Treponema pallidum in secondary syphilis by
PCR and immunohistochemistry. J Invest Dermatol 2007;127: days after hyaluronic acid (Restylane-Medicis Aesthetics)
2345-50. injection.
5. Wenhai L, Jianzhong Z, Cao Y. Detection of Treponema
pallidum in skin lesions of secondary syphilis and characteri-
zation of the inflammatory infiltrate. Dermatology 2004;208:
94-97. We report one patient with erythema and
angioedema-like swelling of the vermilion and cu-
doi:10.1016/j.jaad.2010.11.031 taneous lips (Fig 1) within 12 hours after Restylane
lip injection (Medicis Aesthetics). The procedure was
performed by the patient’s Columbian physician
Angioedema-type swelling and herpes simplex friend in a medical office in the United States.
virus reactivation following hyaluronic acid The patient’s story was substantiated by the
injection for lip augmentation Restylane package and insert (Medicis Aesthetics).
To the Editor: Restylane (Medicis Aesthetics Inc, She reported tingling and pain that preceded the
Scottsdale, AZ) is a hyaluronic acid (HA) dermal swelling by several hours. She presented to the
filler used for soft-tissue augmentation. It is a emergency department where she received an intra-
nonanimal-derived synthetic agent composed of venous methylprednisolone dose. Three days later,
300-m HA particles, cross-linked by ether bonds. she returned to the emergency department with
HA is a glycosaminoglycan distributed throughout worsening pain, swelling, serosanguineous dis-
connective, neural, and epithelial tissue. It serves as charge, and crusting of the vermilion lips (Fig 2).
the viscoelastic network for collagen and elastin fiber Dermatology was consulted. She had profound
binding and provides cell anchor point. Because HA edema of the cutaneous and vermilion lips (worse
is identical in all mammal species, the risk of hyper- on the upper) with multiple monomorphous vesicles
sensitivity is remote. Although adverse reactions can and crusted papules localized to the vermilion lips.
occur with HA derivatives, these are rare.1 Because of our suspicion of herpes simplex virus
e22 Letters J AM ACAD DERMATOL
JULY 2011
(HSV) reactivation, we obtained a swab of the REFERENCES

discharge fluid for bacterial and viral culture and 1. Dover JS, Carruthers A, Carruthers J, Alam M. Clinical use of
Restylane. Skin Therapy Lett 2005;10:5-7.
prescribed oral valacyclovir at 500 mg, by mouth, 2. Leonhardt JM, Lawrence N, Narins RS. Angioedema acute
twice a day for 7 days with a prednisone tapere60 hypersensitivity reaction to injectable hyaluronic acid. Dermatol
mg decreased by 10 mg daily for 6 days. Culture Surg 2005;31:577-9.
proved positive for HSV. We suspected that at least a 3. Bellman B. Immediate and delayed hypersensitivity reactions to
portion of her edema was a result of HSV reactiva- Restylane. Aesthetic Surg J 2005;25:489-91.
4. Food and Drug Administration. Restylane: approved labeling.
tion, but also considered hypersensitivity reaction to Available from: http://www.fda.gov/cdrh. Accessed on February
HA filler. The patient was referred to a cosmetic 22, 2004.
dermatologist for consideration of hyaluronidase 5. Fatahzadeh M, Schwartz RA. Human herpes simplex virus infec-
injection. The patient was subsequently lost to tions: epidemiology, pathogenesis, symptomatology, diagnosis,
follow-up. and management. J Am Acad Dermatol 2007;57:737-63.
6. Fukui M, Whittlesey K, Metcalfe DD, Dastych J. Human mast
HA injection is regarded as a noninvasive and cells express the hyaluronic-acid-binding isoform of CD44 and
effective procedure for soft-tissue augmentation be- adhere to hyaluronic acid. J Clin Immunol 2000;94:173-8.
cause adverse events are rare. Predictable adverse
reactions include erythema, purpura, and swelling doi:10.1016/j.jaad.2010.11.043
limited to the injection site. Other injection-specific
adverse outcomes include bluish Tyndall effect that
represents visible HA seen through the epidermis Erythema gyratum repens without associated
and palpable nodules that occur with depot injec- malignancy
tion.1 Injection-nonspecific reactions previously de- To the Editor: A 48-year-old white man presented with
scribed include immune-mediated angioedema, and a 10-month history of an intensely pruritic annular
immediate and delayed-type hypersensitivity reac- scaling eruption covering his scalp, trunk, and ex-
tions.2,3 Such reactions are characterized by persis- tremities. Lesions first appeared on his abdomen and
tent, nonpitting edema near the injection ranging spread within 2 weeks, covering most of his body
from 10 minutes to 3 weeks3 depending on the surface area. Before presentation he had received
pathogenesis. treatment for presumed psoriasis with midpotency
Although HSV infection is stated as a potential topical corticosteroids and psoralen plus ultraviolet
complication,4 we know of no reports in the litera- A therapy without resolution of symptoms. The
ture of secondary HSV reactivation. Invasive events pruritus was unresponsive to antihistamines. There
are known to cause virus reactivation after previous was no history of treatment with retinoids.
infection.5 Because of the widespread prevalence of Physical examination revealed a well-appearing
HSV,5 patients may benefit from pretreatment with man with erythematous, scaling plaques arranged in
suppressive antivirals. With respect to the patient’s concentric swirls involving 75% of the total body
profound swelling, angioedema-type reactions have surface area (Fig 1). White scale bordered many of
been described; may be related to HA interaction the plaques (Fig 2). The face, oral mucosa, conjunc-
with a cell surface receptor, CD 44, on mast cells; tivae, acral surfaces, nails, and genitalia were normal.
and improve with intramuscular dexamethasone There was no clinically appreciable lymphadenopa-
injection.2,6 As the popularity and ease of use of thy. A full review of systems revealed negative
nonsurgical dermal fillers advances, so does the findings. His medical history disclosed type 2 diabe-
occurrence of injection-specific and injection- tes mellitus and coronary artery disease. His family
nonspecific adverse reactions. history disclosed unspecified maternal lung and
brain cancers. Biopsy specimen revealed a hyper-
Alexis L. Dougherty, MD,a Rashid M. Rashid, MD,
keratotic and acanthotic epidermis with parakerato-
PhD,b and Carolyn A. Bangert, MDb
sis and underlying mild perivascular lymphocytic
Departments of Dermatology at Texas Tech Health infiltrate. Computed tomography scan showed mod-
Science Center, Lubbock,a and University of erate axillary, mediastinal, and groin adenopathy.
Texas Health Science Center, Houstonb Inguinal lymph node biopsy specimen demonstrated
no evidence of malignancy, fungi, acid-fast bacilli, or
Funding sources: None.
clonal immunoglobin gene rearrangement.
Conflicts of interest: None declared. The patient was treated with triamcinolone oint-
ment 0.1% twice daily. His examination at 6 weeks
Correspondence to: Alexis L. Dougherty, MD, 5710
demonstrated near total resolution of lesions. Mild
4th St, Lubbock, TX 79416
erythema with slight scale remained, involving 5% of
E-mail: [email protected] the body surface area, with no visible concentric

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J AM ACAD DERMATOL Letters e21

VOLUME 65, NUMBER 1

histopathologic findings and localization of orga-

(HSV) reactivation, we obtained a swab of the REFERENCES

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