Herpes Zoster_1213 Derm LookAlike 2
Microcystic Lymphatic Malformation_1213 Derm Look1
A young woman presented with a lesion on her left abdomen that had been present since birth. She requested an appointment with a dermatologist because she was bothered by the appearance of the lesion and troubled by the occasional drainage of clear fluid. The lesion had remained stable in size for years, and there was no associated pain or pruritus. No prior treatment had been attempted. History was significant for varicella as a child. Review of systems was otherwise negative. On physical exam, clear and hemorrhagic vesicles were appreciated on the left mid-abdomen.
A woman, aged 62 years, complained of a painful rash. The eruption began as pain and hyperesthesia on her left chest, flank, and back three days prior to presentation. One day earlier, she had noticed a red patch on her left chest that later developed vesicles. OTC hydrocortisone provided no relief. History was significant for primary varicella as a child. Physical examination revealed grouped vesicles on an erythematous base on the left chest. Erythematous edematous plaques were also developing on the left flank and left back.
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Case #1: Microcystic lymphatic malformation
Anomalies of the lymphatic system include lymphedema and lymphatic malformations. Lymphedema is a result of aplasia, hypoplasia, or obstruction of the lymphatic network. On the other hand, lymphatic malformations are caused by hyperplasia of the lymphatic pathways. Lymphatic malformations have been known by many different names, including lymphangioma, cavernous lymphangioma, lymphagioma circumscriptum, and cystic hygroma. More recently, lymphatic malformations have been classified and named based on the size of their malformed channels: microcystic, macrocystic, or combined (microcystic/macrocystic).
Macrocystic lymphatic malformations have previously been known as cystic hygromas and cavernous lymphangiomas in the literature. They are most commonly seen on the neck, axilla, and lateral chest wall and are characterized by large lymphatic channels and cysts. Many cases are diagnosed prenatally by ultrasound and may be associated with karyotype abnormalities, malformation syndromes, or teratogenic agents. Clinically, a large and somewhat translucent soft mass that may be enhanced by transillumination is seen under normal-appearing skin. Intralesional hemorrhage occurs in approximately 35% of lymphatic malformations and may cause the cyst to become tense, tender, swollen, and purple or yellow in color.1 Infection can also complicate as many as 71% of lesions, because the malformed lymphatics are less able to clear foreign material and contribute to antibody production.1 Rarely, vital structures may become obstructed due to the swelling that may be associated with bleeding, infection, or viral illness.
Microcystic lymphatic malformations have been most commonly known as “lymphangioma circumscriptum” in previous literature. These malformations represent microscopic aggregations of ill-defined small lymphatic channels. Lesions commonly appear at birth but may arise at any age. The lesions may occur anywhere on the skin but are commonly seen in the oral mucosa, especially the tongue or cheek. Microcystic lymphatic malformations usually present during infancy as cutaneous plaques or nodules with crops of clear or hemorrhagic vesicles scattered on the surface. The vesicles are often compared to the appearance of frog spawn and may vary in size and number over time. Occasionally, intermittent lymph drainage, inflammation, and secondary infection may occur. Hemorrhage may also occur in these superficial lesions, presenting as intermittent swelling or bruising.
Most lymphatic malformations can be diagnosed by history and physical examination alone. To confirm the diagnosis and define the extent and type of malformation, magnetic resonance imaging (MRI) may be obtained. Ultrasonography is not as informative as an MRI but may be useful, as it does not require sedation.
The differential diagnosis for macrocystic lymphatic malformations include lipoblastoma, teratoma, bronchogenic cyst, branchial cyst, thyroglossal duct cyst, infantile myofibromatosis of intramuscular location. In adults, B-cell lymphoma of the parotid area also must be considered. The differential diagnosis for a microcystic lymphatic malformation includes verruca vulgaris, molluscum contagiosum, herpes simplex, herpes zoster, and epidermal nevus. Lymphatic malformations are usually present at birth or develop shortly thereafter and do not resolve with time; hence, a history that is focused on initial presentation and duration should help to clinch the diagnosis.
Macrocystic lymphatic malformations demonstrate large, irregularly shaped cystic spaces lined by a single layer of endothelial cells in the dermis and in subcutaneous tissue. Smaller, thinner channels may be seen interconnecting the larger channels. The stroma may be loose or fibrotic and scattered aggregates of lymphocytes are often appreciated. Microcystic lymphatic malformations predominantly involve the superficial dermis; however, extension into the dermis and subcutaneous tissue may be seen. Numerous irregular, thin-walled vascular channels that are lined by a single layer of barely visible endothelial cells and varying numbers of smooth muscle cells are seen cutting through collagen bundles. The vascular channels may have sparse proteinaceous material or a few red blood cells, or be empty.
Lymphatic malformations are benign and require no intervention if they are small and/or asymptomatic. Occasionally, bleeding may occur within the lesion, and those patients are best treated with rest. If needed, pain medication or prophylactic antibiotics to prevent infection may be given. For lesions that are symptomatic, cause significant pain or deformity, or threaten vital structures, sclerotherapy (usually performed by an interventional radiologist) is commonly the first-line management. Sclerotherapy causes an inflammatory reaction with subsequent scarring and shrinking of the cyst walls. Sclerotherapy will reduce the size of the lymphatic malformation but will not completely remove it. Sclerosing agents that are used include doxycycline, sodium tetradecyl sulfate (Sotradecol), ethanol, OK-432 (Picibanil) (killed group Streptococcus pyogenes), and bleomycin. The most common complication of sclerotherpay is skin ulceration. Lesions may also recur and oftentimes patients need repeat sclerotherapy over the course of their lifetime. Surgical management may also be considered; however, sclerotherapy has superior efficacy and a lower complication rate than does resection.2 Resection is generally considered a viable option for small, localized, symptomatic lymphatic malformations. Vaporization with a CO2 laser may be successful if deeper components are not present.3 Side effects are infrequent and minor, including dyspigmentation and mild scarring. Pulsed-dye laser and intense-pulsed-light systems also have been reported as effective. Electrodessication may allow symptomatic improvement of superficial lymphatic malformations.4 Radiotherapy has been successful in a few select refractory cases.
Since the patient in this case was cosmetically bothered by her lymphatic malformation, she was referred to interventional radiology for further evaluation and treatment with sclerotherapy.
Case #2: Herpes zoster
Varicella zoster virus (VZV) is the etiologic agent of varicella (chickenpox) and herpes zoster (shingles). Before the development of the varicella vaccine, varicella occurred in 90% of U.S. children prior to age 10 years. Varicella is an eruption characterized by disseminated pruritic vesicles. After a person recovers from varicella, the virus remains dormant and can reactivate years later, causing herpes zoster. An estimated 1 million cases of herpes zoster occur each year. Approximately 20% of healthy adults and 50% of immunocompromised individuals will develop the infection. About half of all cases occur in adults aged 60 years and older; however, younger persons who had primary varicella within the first year of life and those who are immunosuppressed are also at risk. Herpes zoster typically develops only once in a lifetime; severity and incidence increase with age.
After an episode of primary varicella, the virus invades the sensory dorsal root ganglion cells and remains dormant there until reactivation at a later date. Although the exact factors involved in reactivation are unknown, the virus is thought to begin replicating either spontaneously or after an episode of stress, fever, radiation therapy, trauma, or immunosuppression.
While airborne transmission is the usual route of varicella, it can also be spread through direct contact with vesicular fluid. In contrast, herpes zoster can only be transmitted through direct contact with vesicular fluid. Patients who come in contact with the vesicular fluid of herpes zoster will only develop varicella if they have not been previously exposed to the virus. It is important to note that a person with varicella or zoster cannot transmit zoster to another patient, since it represents reactivation of the VZV in a specific host.
Herpes zoster classically occurs unilaterally within a given dermatome. The thoracic dermatome is most commonly involved, followed by the cranial, lumbar, and sacral dermatomes. Patients usually have a one-day to several-day prodrome of intense pain that may be associated with hyperesthesia, tingling, tenderness, or pruritus. The eruption initially presents as erythematous papules and plaques within a given dermatome. Soon thereafter, grouped vesicles develop on this erythematous base. New lesions appear for several days and may become hemorrhagic, necrotic, or bullous. There is often some overflow into the dermatomes above and below the affected area. However, if a patient has visceral involvement and/or develops more than 20 vesicles outside the area of the primary or adjacent dermatomes, he or she is defined as having disseminated zoster. Rarely, a patient may have the intense pain without the eruption; this is termed zoster sine herpete.
Postherpetic neuralgia is the most common sequelae following herpes zoster, with 10% to 15% of all patients developing this complication.5 Other complications include secondary bacterial infections, scarring, ophthalmic zoster, Ramsay Hunt syndrome, motor nerve neuropathy, vasculopathy, pneumonitis, and hepatitis. Complications tend to occur more commonly in those who are older or immunosuppressed.
The differential diagnosis of herpes zoster includes herpes simplex virus (HSV), microcystic lymphangiomas, localized contact dermatitis, and such bacterial skin infections as bullous impetigo and cellulitis. A thorough history and physical examination is usually sufficient to make the diagnosis of herpes zoster. If further testing is needed, a Tzanck smear, direct fluorescent antibody (DFA), and/or lesional biopsy will aid in the diagnosis. Viral cultures have a low yield, confirming the diagnosis in only 60% to 64% of cases.6 The Tzanck smear and DFA have rapid turnaround times, which can be invaluable when making the decision to treat. Only a DFA or immunohistochemical staining will allow distinction between HSV and VZV infections.
Varicella, herpes zoster, and herpes simplex are virtually indistinguishable with routine hematoxylin and eosin (H&E) staining. Intraepidermal vesiculation or ulceration, along with epidermal necrosis and ballooning degeneration, are commonly seen. Herpetic cytopathic changes include pale keratinocytes with steel-gray nuclei, margination of chromatin at the edge of the nucleus, nuclear molding, nuclear dust of neutrophils, multinucleated giant cells, and pink intranuclear inclusions.
The FDA approved the live attenuated VZV vaccine (Oka strain; Varivax) in March 1995. The vaccine is highly effective, with a seroconversion rate in vaccinated children of 96%. If a vaccinated child does subsequently become infected, not only is the primary infection less severe, but there is also a decreased risk of developing zoster.7 Zostavax, the vaccine to prevent herpes zoster, is recommended for adults aged 60 years and older. However, in 2011 the FDA expanded the age indication to include adults aged 50 years through age 59 years. The vaccine was found to reduce the overall incidence of shingles by 51% and the incidence of postherpetic neuralgia (PHN) by 67%.8 FDA-approved treatments for herpes zoster in immunocompetent patients include acyclovir (Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex). Treatment within 72 hours after onset of the first vesicle is most advantageous; however, studies have shown that therapy initiated within seven days also appears to be beneficial.9 Recent studies have shown that the initiation of gabapentin (Horizant, Neurontin) along with valacyclovir may be beneficial in reducing the incidence of postherpetic neuralgia.10 For immunocompromised patients and those with disseminated disease, intravenous acyclovir is the preferred treatment.
The woman in this case was treated with valacyclovir and gabapentin, resulting in resolution of the rash and no incidence of PHN.
Kerri Robbins, MD, is an instructor in the Department of Dermatology at Baylor College of Medicine in Houston.
- Padwa BL, Hayward PG, Ferraro NF, Mulliken JB. Cervicofacial lymphatic malformation: clinical course, surgical intervention, and pathogenesis of skeletal hypertrophy. Plast Reconstr Surg. 1995;95:951-960.
- Smith MC, Zimmerman MB, Burke DK, et al. Efficacy and safety of OK-432 immunotherapy of lymphatic malformations. Laryngoscope. 2009;119:107-115.
- Savas JA, Ledon J, Franca K, et al. Carbon dioxide laser for the treatment of microcystic lymphatic malformations (lymphangioma circumscriptum): a systematic review. Dermatol Surg. 2013;39:1147-1157.
- Emer J, Gropper J, Gallitano S, Levitt J. A case of lymphangioma circumscriptum successfully treated with electrodessication following failure of pulsed dye laser. Dermatol Online J. 2013;19:2. Available at escholarship.org/uc/item/63v8s62s.
- Hope-Simpson RE. Postherpetic neuralgia. J R Coll Gen Pract. 1975;25:571-575. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC2157719/.
- Solomon AR, Rasmussen JE, Weiss JS. A comparison of the Tzanck smear and viral isolation in varicella and herpes zoster. Arch Dermatol. 1986;122:282-285.
- Hayward A, Villanueba E, Cosyns M, Levin M. Varicella-zoster virus (VZV)-specific cytotoxicity after immunization of nonimmune adults with Oka strain attenuated VZV vaccine. J Infect Dis. 1992;166:260-264.
- Centers for Disease Control and Prevention. Herpes zoster vaccination information for health care professionals. Available at www.cdc.gov/vaccines/vpd-vac/shingles/hcp-vaccination.htm.
- Decroix J, Partsch H, Gonzalez R, et al. Factors influencing pain outcome in herpes zoster: an observational study with valaciclovir. J Eur Acad Dermatol Venereol. 2000;14:23-33.
- Lapolla W, Digiorgio C, Haitz K, et al. Incidence of postherpetic neuralgia after combination treatment with gabapentin and valacyclovir in patients with acute herpes zoster: open-label study. Arch Dermatol. 2011;147:901-907. Available at archderm.jamanetwork.com/article.aspx?articleid=1105538.
All electronic documents accessed November 15, 2013.