Collection of Conditions Affecting the Hands

Polydactyly

Author:
Steven N. Glavas, DO, MPH
Michigan State University College of Osteopathic Medicine, East Lansing, Michigan

Citation:
Glavas SN. Polydactyly. Consultant. 2017;57(9):553-554.

A 55-year-old man presented for a routine physical examination. His past medical history was significant for hypertension, obesity, and low back pain. His blood pressure was controlled with hydrochlorothiazide, 25 mg once daily.

Physical examination. The patient’s vital signs were stable at presentation. Physical examination findings were essentially benign, other than 2 small fleshy lesions that were symmetrically located adjacent to the fifth metacarpophalangeal joints bilaterally (Figures). Upon further inquiry, the patient remembered having visited his pediatrician as a child for treatment that had included suture ligation. This had resulted in a dramatic reduction in the girth of these lesions.

The lesions were determined to be related to the childhood treatment of type 1 postaxial polydactyly.

Discussion. Polydactyly is one of the most common congenital hand deformities.¹ Typically, this condition arises from single gene mutations. Other factors such as nutrition and environment may play a role in the increased risk of polydactyly.²

The appearance of polydactyly can vary in morphology from subtle to obvious. It may present as symmetric or unilateral deformities. The lesions may occur on the radial or ulnar side of the hand or on the tibial or fibular side of the foot. Of these, ulnar lesions are most common. Furthermore, the composition of the lesions may or may not include osseous structures.

Polydactyly is classified into 3 subtypes based on description and location. Lesions involving soft tissue only are categorized as type 1, lesions with some osseous structure are categorized as type 2, and supernumerary digits, or complete accessory digits, are categorized as type 3 lesions.

Polydactyly lesions are further categorized as either preaxial—those on the radial side of the hands or the tibial side of the feet—or postaxial—those on the ulnar side of the hands and fibular side of the feet. Preaxial lesions of the hand are far more common than postaxial lesions of the hand.³

The treatment of polydactyly varies according to subtype. Type 1 lesions are typically removed using suture ligation,⁴ as in our patient’s case. Removal of supernumerary digits requires complete amputation.

Treatment complications can include infection, bleeding, abscess, and traumatic neuroma formation.^5,6 

REFERENCES:

1. Graham TJ, Ress AM. Finger polydactyly. Hand Clin. 1998;14(1):49-64.
2. Chung J, Nam IW, Ahn SK, Lee SH, Kim JG, Sung YO. Rudimentary polydactyly. J Dermatol. 1994;21(1):54-55.
3. Gawlikowska-Sroka A, Tudaj W, Czerwiński F. A and B preaxial polydactyly with syndactyly of feet and hands in the same person—a case report. Adv Med Sci. 2009;54(2):305-307.
4. Mullick S, Borschel GH. A selective approach to treatment of ulnar polydactyly: preventing painful neuroma and incomplete excision. Pediatr Dermatol. 2010;27(1):39-42.
5. Klaassen Z, Shoja MM, Tubbs RS, Loukas M. Supernumerary and absent limbs and digits of the lower limb: a review of the literature. Clin Anat. 2011;​24(5):570-575.
6. Jafari D, Sharifi B. A variant of mirror hand. A case report. J Bone Joint Surg Br. 2005;87(1):108-110.

NEXT: Plant Thorn Tenosynovitis

Plant Thorn Tenosynovitis

Authors:
Lynsey A. Seim, MD, and Harvey D. Cassidy, MD
Mayo Clinic, Jacksonville, Florida

Citation:
Seim LA, Cassidy HD. Plant thorn tenosynovitis. Consultant. 2017;57(9):554-557.

A 58-year-old man, right-hand-dominant, presented with a 5- to 6-week history of persistent pain and swelling along the flexor aspect of his left index finger (Figures 1 and 2). He also had a recent history of malaise and decreased exercise stamina. There was no history of trauma or any history of penetrating injuries to the finger prior to the onset of swelling, although the patient readily admitted to consistently sustaining small injuries of his hands in the course of his activities as an avid gardener.

Figure 1: At initial evaluation, marginal swelling was noted along the flexor aspect of the left index finger, with no signs of trauma.

Figure 2: Comparison of the patient’s hands at presentation, with minimal swelling of the left index finger appreciated.

History. Approximately 1 week after the onset of swelling, he had presented to his primary care physician, who had diagnosed overuse tenosynovitis and had prescribed a short course of corticosteroids. At a follow-up visit with his primary provider 10 days later, the pain and swelling had not improved. Given the consistent small injuries to his hands, infection was considered, and a regimen of oral antibiotics was initiated. Again, no improvement was appreciated. The patient also had been taking over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs), which had not led to a reduction in the pain or swelling.

Diagnostic tests. The patient’s primary care physician referred him for magnetic resonance imaging (MRI), the results of which revealed marked signal abnormality with prominent enhancement that extended along the length of the visualized flexor tendon of the digit (Figure 3). Involvement of the volar subcutaneous tissues from the metacarpophalangeal joint to the proximal interphalangeal joint was appreciated, but no fluid collections to suggest an abscess were noted, nor was a thorn visualized. Consultation with orthopedic surgeons raised concern for an atypical mycobacterial infection, and the patient was referred to an infectious disease specialist. Possible flexor tenosynovectomy with synovial biopsy and cultures also was considered.

Figure 3: MRI scans showing signal abnormality and enhancement along the flexor tendon of the left index finger.

An infectious disease specialist evaluated the patient in conjunction with a hand surgeon, and given the patient’s history of generalized malaise and decreased exercise stamina, it was decided that he should proceed with surgical debridement to obtain appropriate cultures and to improve the future function of the finger. Results of a complete blood cell count, erythrocyte sedimentation rate, a chemistry panel, chest radiography, electrocardiography, urinalysis, a C-reactive protein test, and fungal and sporotrichosis serology tests were all unremarkable or negative for infection.

Treatment. Upon surgical examination, the area was debrided, and a palm thorn was found within the flexor tendon sheath of the left index finger (Figures 4 and 5) and was removed. Histology test results of the removed tissue revealed synovium with acute and chronic inflammation and a focal histiocytic reaction. All stains and culture test results for bacterial, fungal, and acid-fast organisms were negative.

Figure 4: Surgical debridement of the flexor tendon, with no immediate findings noted.

Figure 5: Further examination revealed a retained plant thorn along the flexor tendon sheath.

Outcome of the case. Physical therapy was initiated to improve motor function, with excellent results. The patient now has full function of his digit. Despite being advised against doing so, he continues to garden without the use of protective gloves.

Discussion. Plant thorn tenosynovitis is an inflammatory reaction to retained material from a plant. This is often an overlooked diagnosis in cases of monarthritis, particularly in Southern California and the US Southwest, which have an abundance of palm tree thorns. Yucca, mesquite, hawthorn, ougainvillea, sentry plant, blackthorn, rose thorn, sentinel palms, and other thorny plants also have been implicated in foreign body reactions of the joints and should be considered.¹ Usually this is an aseptic process,² although associated infections with Yersinia enterocolitica, Pantoea agglomerans, and bacteria in the Enterobacteriaceae family have been reported. Fungal infections such as sporotrichosis, histoplasmosis, blastomycosis, and coccidioidomycosis should also be considered in the differential diagnosis.³

The type of thorn, the depth of penetration, contamination of the wound, and the age of the patient contribute to the pathophysiologic process and presentation. The type of thorn may play a role due to the varying chemical compositions. The depth of penetration and the nature of the tissue involved are relevant due to the ability of the thorn to lodge into the affected tissues and tendon sheaths. More-superficial wounds typically do not induce such a large inflammatory response as noted in our patient’s case. The age of the patient is significant given the lessened resistance of the tissues and bones in children and the consequent potential for increased depth of penetration.⁴ Moreover, the majority of reported cases involve children, most often the knee joint.

Aerobic and anaerobic bacterial, fungal, and mycobacterial cultures should be obtained to establish a specific diagnosis of contamination of the wound in chronic tenosynovitis. Microscopic examination of inflamed tissue characteristically reveals foreign body granuloma of the giant cell type along with inflammation. Thorns may also be seen, with thick cell walls appreciated. Pathology test results can clinch the diagnosis.¹

The diagnosis of plant thorn tenosynovitis is often delayed, because the history and initial injury is often forgotten or unknown. Clinical and laboratory evaluation must distinguish it from septic arthritis, juvenile rheumatoid arthritis (in children), pigmented villonodular synovitis, transient synovitis, and posttraumatic synovitis.¹ Evaluation should include a detailed history, culture specimens from the joint or synovium aspirate, and assessment of blood inflammatory markers (white blood cell count and erythrocyte sedimentation rate). Plain radiographs are often unrevealing; they sometimes may reveal joint effusions, periarticular erosions, or a periosteal reaction but may not show any plant material. It has been estimated that only 5% to 15% of organic foreign material will be seen on plain radiographs.⁵ However, ultrasonography (US) and MRI have been successfully used to elucidate the diagnosis and to localize the offending foreign body preoperatively.

US is particularly useful in the assessment of possible plant thorn tenosynovitis and is considered the diagnostic modality of choice.⁶ It may aid in the determination of the depth, size, shape, and position relative to other anatomical structures. The modality is often considered operator-dependent, affecting its overall sensitivity; this limitation can be obviated with the use of power Doppler imaging and identification of the hypoechoic halo.^5,7 Power Doppler can also depict reactive hyperemia secondary to inflammatory changes. Given these considerations, the sensitivity of US for detection of soft-tissue foreign bodies has been estimated at 95% to 100%, while the specificity ranges from 89% to 100%.^5,7 US has also been used preoperatively and intraoperatively to reduce patient morbidity by reducing incision size and depth of dissection.⁵

MRI is often used to exclude septic arthritis with underlying osteomyelitis. MRI may be used to delineate soft tissues and to localize the nonradiopaque thorns within tissues. However, it is not considered the diagnostic modality for plant thorn tenosynovitis, nor have any surgically proven cases of plant thorn synovitis been reported in which the thorn was identified using MRI.⁶ US is the modality of choice over MRI for a variety of reasons.⁸ MRI may not be available in a timely manner, and many patients cannot complete the procedure for various reasons. Also, MRI cannot be as easily placed on the area of concern to delineate the etiology of the pain. Finer details, including vascular structures, may be easier to appreciate on US relative to MRI. MRI is best considered as a complementary procedure to US when the clinical question has not been adequately answered by other modalities.⁸

Computed tomography has been used in suspected cases of plant thorn tenosynovitis, but its sensitivity is less than that of US and MRI in detecting the thorn, and it exposes the patient to unnecessary radiation.⁹

Numerous treatments have been suggested for chronic plant thorn tenosynovitis, but timely identification and removal of the offending thorn are recommended to induce complete healing and to prevent further destruction of the tendon and tendon sheath and/or loss of function in the affected site. Treatments include irrigation of the joint with large volumes of saline, and synovectomy in cases that fail to respond to conservative treatment to remove all toxic or inflammatory material. In 5 of 7 cases reported by Ramanathan and Luiz,¹⁰ large-volume irrigation of the joint was curative; however, the preference in other literature sources^1,2,4,11,12 is for synovectomy.

Antibiotics may be useful in the treatment of a contaminated wound, and NSAIDs serve to transiently reduce inflammation. However, once each of these treatments has ceased, the patient will often present with relapsing arthritis until the offending foreign body has been removed. 

REFERENCES:

1. Cahill N, King JD. Palm thorn synovitis. J Pediatr Orthop. 1984;4(2):175-179.
2. Baskar S, Mann JS, Thomas AP, Newton P. Plant thorn tenosynovitis. J Clin Rheumatol. 2006;12(3):137-138.
3. Brady RC, Sommerkamp TG. Thorn-induced Alternaria flexor tenosynovitis of the hand. Pediatr Infect Dis J. 2001;20(11):1097-1098.
4. Nyska M, Sperber AD, Howard CB, Nyska A, Dekel S. Ankle extensor tendon synovitis due to a date palm thorn. Foot Ankle. 1989;10(3):180-183.
5. Davae KC, Sofka CM, DiCarlo E, Adler RS. Value of power Doppler imaging and the hypoechoic halo in the sonographic detection of foreign bodies: correlation with histopathologic findings. J Ultrasound Med. 2003;22(12):1309-1313.
6. Mangat P, Jawad ASM. A case of rose thorn tenosynovitis. Grand Rounds. 2007;7:16-17.
7. Halaas GW. Management of foreign bodies in the skin. Am Fam Physician. 2007;76(5):683-688.
8. Nazarian LN. The top 10 reasons musculoskeletal sonography is an important complementary or alternative technique to MRI. AJR Am J Roentgenol. 2008;190(6):1621-1626.
9. Stevens KJ, Theologis T, McNally EG. Imaging of plant-thorn synovitis. Skeletal Radiol. 2000;29(10):605-608.
10. Ramanathan EB, Luiz CP. Date palm thorn synovitis. J Bone Joint Surg Br. 1990;72(3):512-513.
11. Chow D, Cooke TD, Feltis T. Thorn-induced synovitis. CMAJ. 1987;136(10):​1057-1058.
12. Karshner RG, Hanafee W. Palm thorns as a cause of joint effusion in children. Radiology. 1953;60(4):592-595.

NEXT: Phytophotodermatitis

Phytophotodermatitis

Authors:
Lisa Ousley, DNP; Candice Short, DNP; and Retha Gentry, DNP
East Tennessee State University, Johnson City, Tennessee

Citation:
Ousley L, Short C, Gentry R. Phytophotodermatitis. Consultant. 2017;57(9):557-559.

A 20-year-old woman presented in moderate distress with extensive painful blisters and swelling of the hands and fingers that had developed overnight.

History. The patient reported that the previous evening, while visiting her parents’ home, she had watched television and had eaten dinner. Later in the evening, she had used a personal tanning bed for 10 minutes, then showered and gone to bed, at which time she reported having been well. She awoke that morning with redness, swelling, blisters, and a painful tingling and burning on her hands.

Upon further questioning, the patient recalled having squeezed several limes before dinner to make a pitcher of limeade. She had used a manual juicer, and her hands had been exposed to the citrus juice. She had washed her hands with soap and water afterward. Approximately 3 hours later, she had lain in the tanning bed for 10 minutes.

Physical examination. On physical examination, both of the patient’s hands and her phalanges were edematous. Greater than 50% of the dorsal aspect of her hands displayed an asymmetric erythematous base with numerous vesicles and bullae, a few of which had ruptured (Figures 1 and 2).

Based on the patient’s history, we made a diagnosis of phytophotodermatitis.

Discussion. Phytophotodermatitis is a cutaneous photochemical reaction that can affect any skin type. The cutaneous reaction is provoked by exposure to phototoxic plant substances called furocoumarins (psoralen isomers) and the activation of long-wave UV-A radiation that damages the epidermal cells.¹ The skin reaction can vary from asymptomatic erythema and a painful maculopapular rash to the formation of severe bullae. Presentations also can include pain from sunburn and linear rash (nonserpiginous), with or without hyperpigmented tracks, in which the hyperpigmentation (caused by an increase in melanin deposition) may persist for weeks to months.^1,2

Several plants and/or their fruits or roots can cause phytophotodermatitis, including parsnip, celery, dill, fennel, parsley, hogweed, carrot, Queen Anne’s lace, and citrus fruits (of which limes are the most common cause of phytophotodermatitis). The condition can develop after handling the plant, fruit, or root vegetable; with ingestion or use of plant-derived medications or products; and after incidental contact during hiking, jogging, or other outdoor activities.³

In our patient’s case, lime juice permeated the skin and became the photosensitizer, creating the exaggerated burns after subsequent UV-A exposure in the tanning bed.

Although the psoralen-induced cutaneous reaction typically is delayed by 24 hours and maximizes between 36 and 72 hours after UV-A exposure,⁴ our patient’s reaction was delayed only by approximately 12 hours.

Differential diagnosis. The clinical presentation of phytophotodermatitis varies greatly in lesion type and severity, making diagnosis challenging. The differential diagnoses can be extensive. In our patient, allergic contact dermatitis was considered based on the reported exposure to limes and their juice. Allergens can provoke a severe cutaneous reaction with erythema, edema, blistering, and bullae formation. Allergic contact dermatitis was excluded only after the consideration of UV-A exposure.

Cellulitis was included in the differential based on the magnitude of the edema and erythema but was excluded as a primary diagnosis because of the abrupt formation of vesicles and bullae. Chemical burns were considered based on the presence of erythema, well-demarcated lesions, vesicles, and bullae; however, this diagnosis was ruled out given that her only chemical exposure had been lime juice.

A pemphigus disorder was considered based on the abrupt formation of blisters. The 2 main types, pemphigus vulgaris and pemphigus foliaceus, were ruled out, because pemphigus vulgaris generally starts in the mouth, and pemphigus foliaceus tends to be pruritic rather than painful. Both pemphigus varieties tend to occur in middle-aged or older adults.⁵ Bullous pemphigoid is a rare condition that causes large, fluid-filled blisters to develop primarily along skin folds.⁶ Bullous pemphigoid is most common in people older than age 60.⁶

Infectious lymphangitis was considered, given the location of the insult, the possibility of exposure, and the abrupt symptomology. This diagnosis was ruled out based on negative lymphatic system findings.

The possibility of domestic abuse was included based on the specific physical presentation and the nonspecific supporting history of a known exposure. This diagnosis was ruled out based on the patient’s denial of abuse. It is valuable to mention that child abuse has been incorrectly diagnosed in cases of phytophotodermatitis. Examples of the physical presentation of phytophotodermatitis mimicking child abuse include the presence of handprint patterns on a child’s skin occurring after contact with the hands of an adult who is squeezing or cooking with limes, or linear drip patterns on a child’s hands and arms occurring after the child consumes lime juice popsicles.⁷

Treatment. Most cases of acute phytophotodermatitis require only symptomatic treatment. However, our patient’s severe case required topical and systemic treatment. Wound care included skin care with saline rinse, the topical application of silver sulfadiazine cream, 2%, and dressing of the hands and fingers twice daily. A 7-day course of oral prednisone, 40 mg, was prescribed, and oral hydrocodone/acetaminophen, 10 mg/325 mg every 4 to 6 hours as needed, was ordered for moderate to severe pain.

Outcome of the case. The patient’s erythema and edema were relieved within 48 to 72 hours. At a follow-up visit 1 week later, the vesicles and bullae had resolved; Figure 3 reveals the extent of the epidermal and dermal insult. Hyperpigmentation was evident for approximately 6 weeks before also resolving. The patient was educated to apply a minimum of 30 SPF sunscreen when outdoors to prevent further hyperpigmentation. 

REFERENCES:

1. Marcos LA, Kahler R. Phytophotodermatitis. Int J Infect Dis. 2015;38:7-8.
2. Quaak MSW, Martens H, Hassing R-J, van Beek-Nieuwland Y, van Genderen PJJ. The sunny side of lime. J Travel Med. 2012;19(5):327-328.
3. de Almeida HL Jr, Jorge VM. The many faces of phytophotodermatitis. Dermatol Online J. 2006;12(7):8.
4. Greenaway C. A tropical skin eruption. Can J Infect Dis. 2002;13(2):82-142.
5. Pemphigus. Mayo Clinic. http://www.mayoclinic.org/diseases-conditions/pemphigus/home/ovc-20157520. Updated August 4, 2017. Accessed August 21, 2017.
6. Bullous pemphigoid. Mayo Clinic. http://www.mayoclinic.org/diseases-conditions/bullous-pemphigoid/home/ovc-20157298. Updated August 4, 2017. Accessed August 21, 2017.
7. Baugh WP, Barnette D Jr. Phytophotodermatitis. Medscape. http://emedicine.medscape.com/article/1119566-overview. Updated September 8, 2016. Accessed August 21, 2017.

NEXT: Calciphylaxis

Calciphylaxis

Authors:
John Liantonio, MD, and Philip J. Margiotta, MD
Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

Citation:
Liantonio J, Margiotta PJ. Calciphylaxis. Consultant. 2017;57(9):559-560.

A 68-year-old woman with a history of brittle diabetes mellitus and end-stage renal disease (ESRD) that had required hemodialysis for several years presented to the emergency department with severely painful, discolored digits. The patient described sharp pain in her fingers and toes that had worsened over the past several weeks, and she also noticed that the tips of several digits had become purple or black in the past few days.

Physical examination. The patient was a frail woman in no signs of acute distress. Head, eyes, ears, nose, and throat examination findings, as well as cardiac, respiratory, and abdominal examination findings, were within normal limits. On her extremities, she had necrotic-appearing tips to the level of the distal interphalangeal joints of the third and fourth digits of the hands bilaterally (Figures 1 and 2). The plantar surface of the bilateral great toes had a similar appearance. Plain radiographs of the hands showed arteriolar calcification (Figures 3 and 4). Peripheral pulses were intact in all 4 extremities. She had no other significant skin lesions on her legs, buttocks, or abdomen.

Based on the patient’s history and physical examination findings, she received a diagnosis of calciphylaxis.

Discussion. Calciphylaxis, sometimes called calcific uremic arteriolopathy in patients with ESRD, is a disorder that manifests with skin ischemia resulting from calcification of dermal arterioles. The most common clinical presentation is extremely painful, necrotic skin lesions in the regions of greatest adiposity (such as the legs, buttocks, and abdomen) or in areas of low blood supply (such as the tips of digits).¹

The pathophysiology of calciphylaxis begins with calcification of the blood vessel media.² This is thought to be the result of an elevated calcium phosphate product from secondary hyperparathyroidism, hyperphosphatemia, and/or vitamin D administration, as well as a relative deficiency in inhibitors of vascular calcification in patients on hemodialysis or using warfarin. Continued damage to the vascular endothelium causes fibrosis and thrombus formation within the dermal arterioles, eventually leading to ischemia and necrosis of the overlying skin.²

Although calciphylaxis previously had been considered rare, its prevalence may be as high as 3% to 4% in patients with ESRD. Fewer than 50 case reports of calciphylaxis in patients without ESRD have been published. Risk factors include a longer duration of dialysis, hyperphosphatemia, female sex, diabetes, hypercoagulable states, autoimmune or inflammatory disorders, and the use of medications such as warfarin and vitamin D.

Although not performed in our patient’s case, skin biopsy is generally recommended, the results of which will show calcification, fibrosis, and thrombotic occlusion of dermal arterioles in the absence of vasculitic changes. Imaging techniques such as plain radiographs, computed tomography scans, and mammography can demonstrate arteriolar calcification.

Treatment. Calciphylaxis treatment is multimodal. Most patients receive intravenous sodium thiosulfate, administered 3 times weekly for 3 months. Local wound care, including surgical debridement of infected wounds, is a mainstay of therapy. Elevated levels of parathyroid hormone and hyperphosphatemia should be corrected appropriately. Warfarin, calcium, vitamin D supplements, and other medications that may contribute to disease should be discontinued. The prognosis is relatively poor. Few patients respond significantly to any treatment regimen, and infection is common; thus, focus should be placed on wound care and pain management.

Differential diagnosis. Among the differential diagnoses to consider are systemic vasculitis, peripheral arterial disease (PAD), cholesterol embolization, and cellulitis.

Systemic vasculitides often present with systemic symptoms such as weight loss, fever, and fatigue. There is often multiorgan involvement. Physical examination of the extremities may show signs of neuropathy or palpable purpura. Laboratory test results may be positive for antinuclear antibodies or antineutrophil cytoplasmic antibodies. Skin biopsy testing is often definitive.

PAD is caused by atherosclerotic narrowing, most commonly of the aorta or arteries of the lower extremities. There typically is a subacute-to-chronic progression of disease, from claudication to eventual limb-threatening ischemia with possible ulceration and gangrene.

Skin manifestations of cholesterol embolization may include livedo reticularis (mottled skin, usually on the lower extremities, that blanches with pressure) or blue toe syndrome, primarily following arteriography or intravascular instrumentation (such as catheterization). The symmetric pattern involving multiple digits seen in our patient made this diagnosis less likely.

Cellulitis classically presents with skin warmth, erythema, and edema, most commonly in the lower extremities. Anaerobic bacteria, such as Clostridium species, can cause gangrenous cellulitis; however, the symmetric pattern involving multiple digits in both the upper and lower extremities seen in our patient made a cellulitis diagnosis less likely.

Outcome of the case. During the course of her hospital stay, the patient became acutely ill, with significant respiratory failure and hypotension, and she was no longer able to undergo dialysis. Following many discussions between the team and the patient’s family, she was transitioned to comfort-focused care and was sent to hospice. 

REFERENCES:

1. Nigwekar SU, Kroshinsky D, Nazarian RM, et al. Calciphylaxis: risk factors, diagnosis, and treatment. Am J Kidney Dis. 2015;66(1):133-146.
2. Weenig RH. Pathogenesis of calciphylaxis: Hans Selye to nuclear factor κ-B. J Am Acad Dermatol. 2008;58(3):458-471.