Nodules on the ear - Clinical Advisor

Nodules on the ear

Slideshow

  • Case #1

    April 2015 Dermatology Look-Alikes

    Case #1

  • Case #2

    April 2015 Dermatology Look-Alikes

    Case #2

Case #1

A woman, aged 24 years, presented with two smooth, skin-colored nodules of approximately 5 mm in size on the right superior earlobe extending down the helix of the ear. The lesions were initially pruritic and red and slowly grew over the three months before she came in. She reported that most of the nodules were painful at the time of the clinic visit. The patient said that she had gotten her ears pierced two weeks before the nodules appeared but had to take the earrings out after one month because of how large the nodules became.



Case #2

An 18-year-old female who recently emigrated from India presented with nodules distributed along the bilateral ears. These had been present for the last six months. She also had papules on the trunk and extremities. She reported that the lesions were numb and that she was also experiencing numbness on her hands and feet. She said that her younger brother used to have similar skin lesions and while she could not recall what disease he had, she did report that her brother’s hands and feet are now permanently numb.


This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read Scaly lesions on the palms and soles and Telangiectatic macules on the right chest
. Then take the post-test here.


This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read Scaly lesions on the palms and soles and Telangiectatic macules on the right chest
. Then take the post-test here.Case #1Keloids are benign fibroproliferative lesions resulting from...

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This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read Scaly lesions on the palms and soles and Telangiectatic macules on the right chest
. Then take the post-test here.


Case #1

Keloids are benign fibroproliferative lesions resulting from abnormal wound healing following even minor skin trauma in genetically susceptible individuals. First described in 1700 BC, the term keloid originated from the Greek chele, meaning “crab claw,” for the manner in which the lesions grow laterally into normal tissue.1 In contrast to hypertrophic scars, which stay within the boundaries of the original wound, keloids grow invasively into surrounding healthy skin.2,3 Keloids can be painful and functionally disabling, causing patients both physical and psychological distress.3

Keloids appear with higher frequency in darkly pigmented individuals, with an incidence of 16% in black Africans.2 The incidence of keloids peaks between 10 and 30 years of age; this is possibly explained by the increased rate of collagen synthesis in the young and the greater tension exerted on youthful skin when compared with older, more redundant skin.4 Keloids are more commonly reported in females, which is likely a result of more frequent skin piercings and greater cosmetic concern.1

The pathogenesis of keloid formation is incompletely understood, but is considered to be the result of an abnormal wound healing process.3 Keloids can develop following injury to the skin, including surgery, ear piercings, lacerations, tattooing, vaccinations, insect bites, and any condition resulting in skin inflammation, such as acne or herpes zoster.5 In normal scarring after birth, the number of inflammatory cells and fibroblasts decreases as the healing process proceeds. Following the organization of collagenous matrix into cross-linked bundles, proteases remodel the extracellular matrix in a process carefully regulated by growth factors with negative feedback to prevent pathological scarring.2

In contrast, persons with keloids demonstrate aberrant expression of some growth factors, including transforming growth factor beta, which promotes the chemotaxis of fibroblasts to the site of injury such that collagen synthesis is increased by a factor of 20.4,6 Keloidal fibroblasts exhibit a fourfold increase in the rate of fibronectin biosynthesis compared to fibroblasts from normal dermis.7 Simultaneously, the production of matrix metalloproteinases, which normally support matrix breakdown and remodeling of the scar, is decreased in keloids.4 Several genes related to apoptosis have also been found to be over-expressed in keloidal fibroblasts, supporting the idea that dysregulation of apoptosis may contribute to keloid formation.8 Other factors that have been implicated in keloid formation include hormones and immune reactions to sebum.2,5 It appears that multiple genes impart susceptibility to keloid development; some studies have described a positive association between keloids and certain haplotypes of histocompatibility leukocyte antigen.2,6

Clinically, keloids present as firm pruritic nodules that are associated with restriction of movement in the region of the wound. Most keloids develop within one year after local trauma, although antecedent injury is not often identified.1,2 Initially, these lesions have a pink or red telangiectatic appearance, but they become skin-colored over time. When fully developed, they are firm to palpation with a smooth surface and range in size from millimeters to that of a football. Unlike hypertrophic scars, which typically reach a certain size and stabilize, keloids continue to grow beyond the original wound margin into adjacent normal skin.2,4 They usually lack hair follicles and other functioning adnexal glands.5 Keloids favor sites of increased wound tension, such as the upper trunk, but they are also common on the earlobes; these lesions rarely appear on the palms and soles.2 Genital keloids have been reported subsequent to circumcision, and multiple cases of corneal keloids have resulted in a history of keloids being considered a contraindication to performing laser-assisted in situ keratomileusis (LASIK) for myopia.6

Examples of skin injuries that initiate keloid formation in susceptible individuals

Surgery
Ear piercing
Lacerations
Tattoos
Vaccinations
Insect bites
Conditions resulting in skin inflammation such as acne or herpes zoster

The diagnosis of keloids is clinical. Histopathology reveals thick hyalinized collagen bundles in a haphazard array with mucinous ground substance and an increased number of fibroblasts. The differential diagnosis includes hypertrophic scars, which, by contrast, have collagen bundles oriented parallel to the skin surface. Spindle cell tumors and desmoplastic melanoma may be distinguished by immunohistochemical stains for CD34 and S-100, respectively. Lobomycosis, an infection of Lacazia loboi, may be diagnosed by microscopy, periodic acid-Schiff stain, or silver staining. Lobomycosis is spread by infected dolphins. The differential should also include xanthoma disseminatum and keloidal forms of scleroderma and morphea.4

Keloids are a therapeutic challenge. There is no universally accepted treatment protocol. Surgical excision combined with postoperative radiation treatment has produced the best prospective outcomes, although there have been no randomized controlled trials to date.4 A recurrence rate of 55% to 100% has been reported after removing keloids with surgical excision alone.9,10 Other treatment options include intralesional injections of corticosteroids, which may soften and flatten the keloids but not facilitate their complete regression, as well as intralesional 5-fluorouracil and interferon alpha-2b.4,5 Several studies have suggested that application of silicone gel sheeting to keloids improved scar thickness and color, but with weak evidence.11 Ultimately, prevention of future wounds is key. 


Our patient requested a biopsy to confirm the diagnosis. Histopathology revealed thick hyalinized collagen bundles in a haphazard array. Treatment consisted of surgical excision followed by radiation, which resulted in excellent improvement in the size of the lesions. 


Case #2

Leprosy is a slowly progressive granulomatous disease with prominent involvement of the skin and peripheral nerves.4 The causative bacterium, mycobacterium leprae, is an acid-fast bacillus and obligate intracellular parasite that infects macrophages and Schwann cells.12 Known to exist as early as 600 BC in India, leprosy has been historically considered a deforming and stigmatizing disease, although rarely a cause of mortality.4

Once widely distributed in Europe and Asia, leprosy now occurs primarily in warm and temperate regions of developing countries. More common in males than females, the incidence of leprosy peaks in young adulthood.12 The incubation period between infection and visible disease varies widely but is usually four to 10 years, and a low rate of transmission may occur for decades, as shown by the incidence of new cases in regions with long-standing leprosy control programs.13M. leprae is likely spread by respiratory droplets, with bacterial DNA detectable in nasal secretions. Proximity to infected persons is the most important determinant of transmission; the risk of acquiring disease from household contacts is 25%.4,12

Rare cases of leprosy have been reported as contracted in the United States, primarily through contact with armadillos which may transmit the organism. 


The pathogenesis of leprosy is poorly understood, but evidence suggests the manifestations of infection depend on the host’s capability to develop an effective cell-mediated immune response to M. leprae.13 Depending on the level of immunity, the disease can progress without restraint or limit itself. A predominantly T helper type 1 (Th1) cell response, as seen in patients with tuberculoid leprosy, that is mediated by the cytokines interleukin (IL)-1 and IL-12 and tumor necrosis factor alpha is associated with few skin lesions and a low burden of organisms. At the other end of the spectrum, lepromatous leprosy is characterized by the uncontrolled proliferation of bacilli with many lesions and extensive infiltration of the skin and nerves.12 These patients have a Th2 cell response with IL-4, IL-5, IL-10, and IL-13.4 Borderline leprosy encompasses phenotypes falling somewhere in the middle of the spectrum. 


The unique predilection of M. leprae for Schwann cells is determined by the bacterium’s binding to laminin-2, a component of the basal lamina restricted to the Schwann cells of peripheral nerves. T cells recognize mycobacterial antigens in the nerve and initiate a chronic inflammatory response, leading to swelling in the perineurium, ischemia, and fibrosis with axonal death.12 The mycobacterial cell wall contains phenolic glycolipid 1, which may contribute to disease by suppressing the T-cell response and producing interferon-gamma. Susceptibility to severe infection appears to correlate with specific genetic factors, such that individuals with human leukocyte antigen (HLA)-DR2 and HLA-DR3 usually develop the tuberculoid form of leprosy, whereas those with HLA-DQ1 acquire lepromatous leprosy.4

The clinical presentation of leprosy depends on the degree of cell-mediated immune response to M. leprae, reflected by the spectrum of lepromatous, tuberculoid, and borderline phenotypes. Initially the onset is insidious, first affecting peripheral nerves with numbness or painful paresthesias and transient hypomelanotic macules as it infects the skin.13 In lepromatous leprosy, the lesions enlarge and coalesce, resulting in symmetrically distributed nodules and raised plaques most commonly involving the face, buttocks, and lower extremities.12,13 Saddle nose deformities and infiltration of the earlobes lead to characteristic leonine facies.4 Anesthesia in a stocking or glove distribution may develop, often with enlargement of peripheral nerves. Due to involvement of the facial and trigeminal nerves, lagophthalmos or corneal and conjunctival anesthesia may develop.4,12 Neuropathic changes result in muscle atrophy, flexion contractures of the fourth and fifth fingers, and secretory disturbances. In contrast, tuberculoid lesions consist of atrophic hypopigmented annular macules with raised edges, asymmetrically distributed on the posterolateral extremities, back, and face. The lesions are devoid of sweat glands and hair follicles.4,13 Borderline leprosy exhibits intermediate features, and patients may show slow change towards the lepromatous pole or spontaneously regress.4,12

Countries in which risk of exposure to leprosy is greater

Angola
Brazil
Central African Republic
Democratic Republic of Congo
Federated States of Micronesia
India
Kiribati
Madagascar
Mozambique
Nepal
Republic of Marshall Islands
United Republic of Tanzania
Source: Hansen’s Disease (Leprosy): Risk of Exposure. Centers for Disease Control and Prevention. Available at cdc.gov/leprosy/exposure. Updated April 29, 2013

The differential diagnosis includes granulomatous conditions such as sarcoidosis, leishmaniasis, and syphilis.13 Hypopigmented macules at initial presentation may mimic tinea corporis or pityriasis alba.4 Lesions on the earlobes may be mistaken for keloids. 


The diagnosis of leprosy is clinical, aided by the finding of acid-fast bacilli on skin smears or biopsy material.12,13M. leprae has not been cultured in vitro, but it grows when inoculated into the foot pad of a mouse. Additional tests include polymerase chain reaction for M. leprae DNA and serology for immunoglobulin M antibodies to phenolic glycolipid 1. Histopathology reveals an extensive cellular infiltrate with macrophages filled with organisms in lepromatous forms and epithelioid cell granulomas forming around dermal nerves in tuberculoid leprosy.13 Of note, leprosy may cause a false-positive Venereal Disease Research Laboratory (VDRL) test and fluorescent treponemal antibody absorption (FTA-ABS) assays for syphilis.4

Multidrug therapy is recommended by the World Health Organization for treatment of leprosy. Lepromatous forms of the disease improve with a regimen of dapsone, clofazimine, and rifampin. Dapsone and rifampin are indicated for tuberculoid leprosy.13 The number of new cases reported each year decreased from more than 500,000 in 2003 to fewer than 250,000 in 2010, reflecting the impact of multidrug therapy.4 Ultimately, however, recognition of the disease in its initial phases is essential in order to reduce the disfiguring consequences of infection. Frequently, reactional states with an acute worsening of symptoms will develop in response to initiation of treatment. Depending on the nature of the reaction, prednisone or thalidomide may be indicated.4

A biopsy from our patient revealed macrophages filled with many acid-fast bacilli. She was diagnosed with lepromatous leprosy. Treatment consisted of dapsone, clofazimine, and rifampin. Despite therapy, the patient’s hands and feet are permanently numb in a stocking distribution.

Lucette Liddell, BA, is a third-year medical student and Maura Holcomb, MD, is a second-year dermatology resident at Baylor College of Medicine in Houston.



This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read Scaly lesions on the palms and soles and Telangiectatic macules on the right chest
. Then take the post-test here.


References 


  1. Berman B, Bieley HC. Keloids. J Am Acad Dermatol. 1995;33(1):117-123. 

  2. Seifert O, Mrowietz U. Keloid scarring: bench and bedside. Arch Dermatol Res. 2009;301(4):259-272. 

  3. Shih B, Bayat A. Genetics of keloid scarring. Arch Dermatol Res. 2010;302(5):319-339. 

  4. Bolognia JL, Jorizzo JL, Schaffer JV, eds. Dermatology. 3rd ed. Philadelphia, Pa.: Elsevier Saunders; 2012.

  5. English RS, Shenefelt PD. Keloids and hypertrophic scars. Dermatol Surg. 1999;25(8):631-638. 

  6. Robles DT, Moore E, Draznin M, Berg D. Keloids: pathophysiology and management. Dermatol Online J. 2007;13(3):9. Available at escholarship.org/uc/item/2m43548r 

  7. Babu M, Diegelmann R, Oliver N. Fibronectin is overproduced by keloid fibroblasts during abnormal wound healing. Mol Cell Biol. 1989;9(4):1642-1650. Available at mcb.asm.org/content/9/4/1642.long

  8. Satish L, Lyons-Weiler J, Hebda PA, Wells A. Gene expression patterns in isolated keloid fibroblasts. Wound Repair Regen. 2006;14(4):463-470. 

  9. Butler PD, Longaker MT, Yang GP. Current progress in keloid research and treatment. J Am Coll Surg. 2008;206(4):731-741. 

  10. Mustoe TA, Cooter RD, Gold MH, et al; International Advisory Panel on Scar Management. International clinical recommendations on scar management. Plast Reconstr Surg. 2002;110(2):560-571. 

  11. O’Brien L, Jones DJ. Silicone gel sheeting for preventing and treating hypertrophic and keloid scars. Cochrane Database Syst Rev. 2013;9:CD003826. Available at onlinelibrary.wiley.com/doi/10.1002/14651858.CD003826.pub3/full

  12. Britton WJ, Lockwood DN. Leprosy. Lancet. 2004;363(9416): 1209-1219. 

  13. Wolff K, Johnson RA, Saavedra AP, eds. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 7th ed. New York, N.Y.: McGraw-Hill Educational; 2013.


All electronic documents accessed on March 30, 2015.



This The Clinical Advisor CME activity consists of 3 articles. To obtain credit, read Scaly lesions on the palms and soles and Telangiectatic macules on the right chest
. Then take the post-test here.


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