`
`Amedcan Academy of Orthopaedic Surgeons Web site: Orthopaedic Knowledge Online Journal2014 I2(8): h tp//orthoporta aao~, ~rg/okolert c e.aspx?
`~r~icl~--0KO Fog060. Accessed August 1, 2014
`
`©2001 - 20’14 by Ihe American Academy c~f Ol~hopaedl¢ Surgeons. "All Rights
`This w~bsile and its ¢onten~s may not he reproduced In whole or In part without wrltte¢~ pe~’missi~n.
`
`Introduction
`
`Orthopaedic surgeons may be the first medical professionals to encounter a skin lesion on a patient’s foot, Early
`identification of the condition causing such a lesion is crucial for initiating its treatment or referring the patient to a dermatologist
`for further management.
`
`To achieve the correct diagnosis of a dermatologic condition of the foot, it may be necessary to evaluate the entire
`cutaneous surface of the foot and integrate the objective findings with the patient’s relevant medical history. Four basic
`features of skin lesions must be noted and considered during the physical examination of a patient: (1) color, (2) morphology,
`(3) configuration, and (4) distribution. In addition, a basic conceptual framework of the nature and causation of various skin
`lesions is helpful in their identification and treatment. Table 1 provides a practical scheme for the classification of dermatologic
`disorders of the foot into the three main categories of: (1) infectious, (2) neoplastic (benign and malignant), and (3)
`inflammatory disorders.
`
`This article Is Intended to provide an overview of the clinical presentation, pathogenesis, diagnostic evaluation, and
`strategies for the general management of common dermatologic conditions of the foot, and dilemmas in the diagnosis of such
`
`conditions.
`
`Table 1: Classification of Derrnatolo£ic Conditions of the Foot
`
`Infectious
`
`Neoplastic
`
`Benign
`
`MaIlgn a n t
`
`Acute paronychla
`
`Warts and clay!
`
`Melanoma
`
`Inflammatory
`
`Cutaneous manifestations of
`diabetes
`
`Tinea pedis
`
`Pyogenic granuloma
`
`Kaposi
`sarcoma
`
`Pernlo
`
`Onychomycosis
`
`Chromoblastomycosis and
`mycetoma
`
`Fibroma
`
`Mucous cyst
`
`GIomus tumor
`
`Longitudinal
`melanonychia
`
`Infections
`
`Rheumatoid papules
`
`Palmoplantar psoriasis
`
`Reactive’ arthritis
`
`Acquired palmoplantar
`keratodermas
`
`Paronychia
`Acute paronychia of the foot is caused by the bacterial pathogens Staphylococcus aureus and Streptococcus
`pyogenes, usually following trauma to the nail folds of the toes. With paronychia, the proximal nail fold is often painful,
`
`erythematous, and swollen, and these symptoms may be associated with a purulent discharge or abscess formation in the
`nai! folds, or I~oth (Figure 1). Recurrent episodes of paronychia should raise the suspicion of herpes simplex virus (HSV)
`
`Page 1 of 14
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`ACRUX DDS PTY LTD. et al.
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`EXHIBIT 1512
`
`IPR Petition for
`
`U.S. Patent No. 7,214,506
`
`
`
`infection.1 If diagnosed at an early stage in its development, acute paronychla without an abscess can be treated with
`
`toplcal antlbiotlcs alone. If an abscess has developed, it should be Incised and drained. Chronic paronychia is usually
`
`caused by Candide albicans and treated with topical imidazoles and corticostercids.2
`
`Flt], 1
`
`Acute pa~nychia, The proximal nail fold of the big toe is erythematous and swollen, with loss of the
`cuticle.
`
`Courtesy of the Dep~trime=nt of Oermstology at the University of Alabama, Birmingham, School of Medicine,
`
`Tines Pedis
`Tinea pedis, also known as athlete’s foot and ringworm of the foot, is the most common dermatophytic infection of the
`foot. The feet are particularly prone to dermatophytlc invasion and growth because they lack sebaceous glands, exist
`much of the time in a moist environment created by occlusive shoes, and often experience damage or trauma to their skin
`barrier.
`
`Four subtypes of tines pedis affect the foot: (1) the moccasin subtype, characterized by plantar erythematous plaques
`covered by hyperkeratotic scales and involving the entire plantar surface of the foot (Figure 2); (2) the vesiculobullous
`subtype, characterized by vesicles and bullae; (3) the interdigital subtype, characterized by scaling and fissures in the toe
`webs, often with maceration; and (4) the ulcerative subtype, marked by ulcers and erosions. The subtle dorsal patch on
`
`the foot with a collarette of scale is a characteristic finding and clue to the diagnosis of tines pedis.3 Technically, infection
`of the dorsal aspect of the foot is considered tinea corporls. The diagnosis of tines pedis can be made with skin scrapings
`treated with potassium hydroxide and subjected to direct microscopic examination and with fungal culture. Topical
`
`treatment with antifungal agents for about 1 month is the mainstay of treatment of tinea pedis.4
`
`Fi~l. 2
`
`Tines pedls (moccasin iype). Scaly erythematous plaqJes wilh sharply defined scalloped borders are
`
`present on the bottom of the foot. Inset: Collarette of scale on a plaque,
`
`Courtesy or’the Department of DermatOlogy at the University of Alabama. Birmingham, ~chool of Madicine.
`
`Onychomycosis
`Onychomycosis is the fungal infection of a fingernail or toenail caused by dermatophytes, nondermatophyte molds, or
`yeasts. The absence of effective cell-mediated immunity at the nai!, a diminished host Immune response, and an
`abnormat nail unit contribute to fungal invasion of the nail. Onychomycosis commonly begins as tines pedis before
`extending to the nail bed, where its eradication is more difficult. The latter site serves as a reservoir for local recurrence or
`
`for spread of the infection to other areas.~
`
`Clinically, four types of onychomycosis are distinguished: (1) distal lateral subungual onychomycosis (Figure 3), with
`invasion via the hyponychium; (2) proximal subungual onychomycosis, with Invasion under the proximal nail fold (common
`in immunocompromlsed hosts); (3) white superficial onychomycosis, with direct invasion of the dorsal nail plate; and (4)
`
`Page 2 of 14
`
`
`
`total dystrophic onychomycosis, which results from the progression of any of the other subtypes or a combination of two or
`more of them. All of the subtypes of onychomycosls may cause an "abnormal nail" with white-to-yellow discoloration,
`onycholysis, crumbling, and thickening; however, only half of abnormal nails have onychomycosis. Psoriasis, lichen
`planus, trauma, and runner’s toe are included In the differential diagnosis of onychomycosis. The diagnosis of
`onychomycosis is confirmed with the KOH (potassium hydroxide) test and microscopic examination, or by culture, or
`
`both.6
`
`Fig. 3
`
`Left, Distolateral subungual onychomycosis. Yellow discokxation of the distal nail plate of the big toe
`
`with onycholysIs, Right, White superficial onychomycosis caused by infection with Fusarium slop,
`
`The distal nail plata shows chalky white discoloration.
`
`Oo~rtesy of the Depadmenl of Dermatology at the University af Alabama, Birmingham. School of Medil~ine.
`
`Oral antifungal agents are the standard of care for this condition, but may have adverse systemic effects. Topical
`antifungal agents (10% efinaconazole, 8% ciclopirox, and others), as wel~ as laser-based therapies, are promising
`
`solutions for the treatment of onychomycosis, although their long-term efficacy remains to be determined.7’6
`
`Chromoblastomycosis and/~ycetoma
`Chromoblastomycosls and mycetoma are ~;hronic fungal infections of the skin and subcutaneous tissues. Both
`conditions are caused by a variety of fungi found in soil, plants, and wood. Infection may begin with inoculation by
`contaminated debris. Although the causative fungi are found frequently in tropical countries in South America, they are
`
`occasionally seen In the United States.9
`
`Mycetomas can be caused by fungi (eumycetomas}, aerobic actinomycetes, or filamentous bacteda
`(actinomycetomas), which enter the skin by direct inoculation. Mycetomas present clinically with swelling, nodules, and
`sinus tracts and a pustular drainage that contains grains consisting of fungal colonies (Figure 4). As the infection
`progresses, adjacent fascia and bony structures may become involved, resulting in osteomyelitis. Mycetomas are Indolent
`and disfiguring, progressing slowly over periods of years. Hlstopathologic examination and culture are necessary to
`
`ensure that the etiologic agent is a mold and not an actinomycete,t0
`
`Fig. 4
`
`Chromoblastomycosis, marked by a dark red graqulomatous nodule over an erythematous base.
`
`Courtesy of the Oepartment of Oermatology at the University of Alabama, Birmingham, School of Medicine.
`
`The typical lesion of chromoblastomycosis is a papule or nodule that progresses over months to a verrucous or
`granulomatous plaque (Figure 5). At an early stage the lesion may resemble a wart, but does not respond to traditional
`therapy. It may later develop an annular appearance as the central portion resolves with scarring. The diagnosis is
`established by histopathologic identification of the causative organism. The treatment of chromoblastomycosis and
`
`mycetoma involves surgical excision followed by systemic antifungal therapy.1°
`
`Page 3 of 14
`
`
`
`Fi~, 5
`
`Mycetoma, consisting era large plantar nodule with pustular drainage and yellow grains,
`
`Ceu~esy of fhe Depadmenf of Oe~’rnatology ai the University of Ahabama. Birmingham, School of Medicine,
`
`,Beni~ln Neoplasms
`
`Warts and Clavt
`Warts (or verrucae vulgaris) are common cutaneous neoplasms caused by the human papilloma virus (HPV), Infection
`
`by the virus occurs through minor abrasions, is promoted by maceration, and is acquired by skin-to-skin contact or from
`
`contaminated surfaces and objects (eg, swimming pools, gymnasium equipment). Autoinoculatlon of the virus from an
`
`infected site Into adjacent skin is frequently observed. Warts present as verrucous, hyperkeratotic, flat.topped papules
`
`(Figure 6). Shaving of the surface of a wart reveals a central core of keratinized debris, punctate bleeding points (black
`
`dots), and dermatoglyphic disruption, and these lesions are often painful when squeezed from the sides. Clavi (or corns)
`
`are well-circumscribed, horny, white-gray or yellow-brown papules that are painful when compressed and may display a
`
`clear center without "black dots" when shaved, A clavus results from an underlying skeletal anatomic defect or repeated
`
`trauma and pressure over a bony prominence from an Ill-fitting shoe or bone malalignment.1t
`
`FiB, 6
`
`Plantar wart, characterized by a verrucous, hyperkeratotic, fiat.topped yellowish papule.
`
`Courtesy of the Department of Derrnatelog’:/at the University of Alabame, Birmingham. School of Medicine.
`
`The diagnosis of a wart or clavus is established clinically, Most warts in immunocompetent patients will regress
`spontaneously within 1 to 2 years and without any treatment. If a wart takes a longer time to regress, or has multiple
`recurrences, immunosuppression or an amelanotic melanoma should be suspected. The most effectiye methods for
`treating any type of wart are cryotherapy with liquid nitrogen, the topical application of salicylic acid, or the use of an
`
`immunomodulator such as imiquimod.12 The treatment goal for symptomatic corns is to provide pressure relief. Diverse
`
`methods have been described, including the use of wider shoes, padding, shaving the lesion, topical application of
`
`salicylic acid, and condyiectomy,13,~4
`
`Pyosenic Granuloma (Botryomycoma)
`Pyogenic granulomas are bleeding, friable, soft, red papulonodules (Figure 7) that grow rapidly over the course of
`
`several weeks. In the feet, they appear, in c~ecreasing order of frequency, within the nail unit (periungually or subungually),
`
`on the toes, or elsewhere. Predisposing factors include penetrating trauma, systemic drug therapy (eg, retinoids, inhibitors
`
`of epidermal growth factor receptor), pregnancy, peripheral nerve damage, ingrown toenails, and frictional onycholysis.~s
`
`The most common treatment of a pyogenio granuloma is surgical excision; case reports have shown response to topical
`
`tlmololIs and 5% imiquimod.17
`
`Page 4 of 14
`
`
`
`Fi~. 7
`
`Pyogenic granuloma on the sole of the foot. marked by a friable, soft, red nodule.
`
`Ccu=lesy of the Department of Dermatology at the University of Alabama. Birmiagharn, School of Medicine
`
`Fibroma
`Fibromas present as asymptomatic, smooth, dome-shaped, pink-to-skin-colored nodules on the dorsolateral aspects
`of the fingers and toes (Figure 8). Periungual and subungual fibromas are usually isolated lesions, but multiple fibromas
`
`occur in 50% to 80% of patients with tuberous sclerosis.18 Periungual fibromas may compress the nail matrix and produce
`
`a longitudinal groove in the nail plate. Subungual fibromas that grow beneath the nail plate cause longitudinal
`erythronychia or onycholysis. Ftbromas follow a benign course and can be removed by surgical excision with or without
`
`phenolization.19
`
`FiB. 8
`
`Fibroma, occurring as a smooth, dome-shaped, pink pedungual nodule. Note the Iongiludinal groove
`
`in the nail.
`
`Courtesy of the 13epadment of Dermatology at the University of Alabama, Birmingham, School of Medicine.
`
`Mucous Cyst (Myxoid Cyst)
`Mucous cysts are the most common tumors of the nails, often occurring in middle-aged women. Their etiology is
`controversial, with some authors maintaining that they are of degenerative odgln and others suggesting that they extend
`
`from the distal interphalangeal joint space. The cysts are soft, skin-colored nodules that develop on the dorsal aspect of
`the distal phalanx of a digit, and may drain a viscous, jelly-like fluid (Figure 9). Some mucous cysts are subungual; if
`
`compression of the nail matrix occurs, it produces nail-plate depression and a longitudinal groove in the nail.2° Subungual
`
`cysts are connected to the distal interphalangeal joint by a tract, and osteoarthritis ef the distal joint is frequently
`
`associated with these lesions.;z0 Treatment options for mucous cysts include sclerotherapy, cryosurgery, and the
`
`intralesional injection of corticosteroids.21 Surgical excision with Joint d6bridement has been reported as a successful
`
`treatment option for mucous cysts, with minimal recurrences.~2
`
`Fi~. 9
`
`A mucous cyst, seen as a s~ft, skin-colored nodule with scale over the dist~l inteq)halangeal ioint of
`
`the second toe.
`
`Ooudesy of the Depadlllen| of Dermatology at the University or Alabama, Birmillgham, School of Med(¢ine,
`
`Page 5 of 14
`
`
`
`Glomus Tumor
`Glomus tumors appear as solitary, subungual, red-bluish macules, often in young female adults. Most of these tumors
`arise from glomus cells of the dermis of the nail bed, although a few may arise from pluripotent mesenchymal cells.
`
`Glomus tumors occur especially In the subungual area of the fingers, but have also been described in the great toe.23
`They are tender to the touch, and may be associated with severe paroxysmal pain in response to temperature changes
`
`(especially cold) and pressure.~’4 Surgical excision Is the preferred treatment of glomus tumors.
`
`Longitudinal Melanonych|a
`Longitudinal melanonychia results from increased melanin deposition in the nail plate and is characterized by one or
`more tan, brown, or black longitudinal streaks (Figure 10). The width of the streaks ranges from a few millimeters to the
`entire width of the nail. Longitudinal melanonychia is commonly observed in older individuals with darkly pigmented skin.
`However, it tan’also be caused by trauma, drugs (chemotherapeutic agents, zidovudine, psora[ens), radiation, pregnancy,
`HIV infection, Addison disease, onychomycosis, a nevus of the nail matrix, melanoma, and nonmelanocytic tumors, such
`
`as onychomatricoma,2~,26
`
`Fig. 10
`
`Longitudinal melanonychia, marked by a dark brown, longitudinal pigmented band on the nail surface
`of the big toe,
`
`Coudesy ef tile Oepadment of De~’ma|oIogy at ~Jle University of Alabama, Birmingham, School of Medicine.
`
`Because the precise etiology of longitudinal melanonychia often cannot be ascertained through only clinical inspection
`and a patient history, melanoma should always be included in the differential diagnosis. A subungual melanoma may
`present as a longitudinal brown to black band in association with hyperplgmentation of the proximal nail fold or
`
`hyponychium (Hutchinson sign). Any lesion for which there is a suspicion of melanoma should be biopsied,z7
`
`Malignant Neoplasms
`
`Melanoma
`Metanoma is responsible for most deaths related to skin diseases. The overarchlng hypothesis for the pathogenesis of
`melanoma is that ultraviolet radiation induces genetic or epigenetic alteratlons in melanocytes, leading to aberrations in
`
`major cell-signaling pathways.28’2s Melanoma affects all age groups, and the risk of its development Is increased in
`
`individuals with lightly pigmented skin, a patient or family history of cutaneous melanoma, inability of the skin to tan, red
`hair, a history of exposure to intense sunlight, psoralen plus ultraviolet A (PUVA) light therapy, the use of a tanning bed,
`
`and immunosuppression.3°
`
`Four major types of cutaneous melanoma have been recognized: (1) superficial spreading melanoma; (2)lentigo
`maligna melanoma; (3) nodular melanoma; and (4) acral lentiginous melanoma. Superficial spreading melanoma is the
`most common type of melanoma in fair-skinned individuals, and presents as a brown-to-black, asymmetric macule or
`papule that may bleed spontaneously. The back and the lower leg are common sites of presentation of this type of
`melanoma. Nodular melanoma presents as a purple or bluish-black nodule on any skin site. Lentigo maligna melanoma
`presents as an asymmetric brown-to-black macule frequently located on sun-exposed skin sites in older individuals. Acral
`lentiginous melanoma is the most common type of melanoma in black, Asian, and Hispanic individuals, and presents as
`
`Page 6 of 14
`
`
`
`an enlarging, hyperpigmented macule on the palms, soles, or digits (Figure 11). This type of melanoma is often diagnosed
`
`at an advanced stage because of the difficulty in distinguishing it from benign lesions and traumatic changes in the skin.31
`
`FiB. 11
`
`The brown-to-black, irregular patch of an acral lentiginous melanoma.
`
`Co~.lrtesy of the Depaltment of De~’l~stology at the Ull~vo(’si~y of Alabama, Birmingham, $cl~oel of Me(l~cine.
`
`Table 2 presents a list of common cutaneous lesions of the foot that may mimio melanoma, The diagnosis of
`melanoma is established histologically, Surgical excision is the treatment of choice for early-stage melanoma, Aggressive
`regimens of chemotherapy and immunotherapeutic regimens are used for treating late-stage melanoma. Protection from
`
`ultraviolet radiation reduces the risk of melanoma,3z
`
`Table 2: Benign Skin Conditions of the Foot That Should Be Differentiated From Melanoma
`
`Condition
`
`Pigmented
`dermatofibroma
`
`Tattoo (medical or
`traumatic)
`
`Subungual
`hematoma
`
`Longitudinal
`melanonychia
`
`Black heel (talon
`hair)
`
`Tinea nigra
`
`Description
`
`Firm, poorly demarcated papule or nodule that dimples downward when compressed
`laterally, Usually <6 mm,
`
`Medical tattoos are characterized by small pigmentary dots, often blue or green, with a
`regular pattern (rectangle). Traumatic tattoos are irregular and their pigmentation may
`appear black,
`
`Red-brown macule or patch. As the lesion grows out from the nail fold, a curving, clear area
`ts seen in the proximal end of the lesion.
`
`See description in text,
`
`Asymptomatic, trauma-induced violet-to-black macules or patches on the posterior heel and
`occurring primarily in athletes.
`
`A single, sharply demarcated, brown-to-gray macule or patch with or without mild scaling.
`No associated symptoms.
`
`Kaposi Sarcoma
`Kaposi sarcoma (KS) Is a spindle-cell malignancy that arises from the vascular endothelium and is associated with
`infection by human herpesvirus type 8 (HHV-8). It is a systemic disease that presents with cutaneous lesions with or
`without internal involvement, Four subtypes of KS have been described: (1) ctassic KS; (2) African endemic KS; (3) KS in
`
`iatrogenically immunosuppressed patients; and (4) AIDS-related KS.33 The cutaneous manifestations of KS are pink-to.
`
`dark violet plaques or nodules, usually located on the lower leg (Figure 12). The diagnosis is established clinically and
`
`histologically, and if internal organ involvement is suspected, imaging should be done.;~4
`
`FiB. 12
`
`The dark red-violet plaque of a Kaposi sarcoma in a patient wih HIV infection.
`
`Courtesy of the Depart=lle~lt of Dermatology at the Unive~’sity of Alabarna, Blrmlngllam, School of Medicine.
`
`Page 7 of 14
`
`
`
`First-line therapy for AIDS-related KS consists of antiretroviral agehts, because in most cases this treatment alone is
`
`associated with improvement. Localized cutaneous KS can be treated with cryotherapy, toplca~ retinolds, and lasers,35
`
`Extensive cutaneous KS and/or ir~ternal disease may require radiation or chemotherapy.36 Systemic therapies that inhibit
`
`angiogenesis or target HHV-8 are under investigation.37
`
`Inflammatory Conditions
`
`Cutaneous Manifestations of Diabetes
`Four diabetic skin conditions are manifested chiefly in the lower extremities: (t) necrobiosis lipoidica; (2) diabetic
`dermopathy; (3) bullosis diabetlcorum (BD); and (4) diabetic ulcer, The first two of these conditions localize predominantly
`to the shins and are therefore outside the scope of this review.
`
`Bullosis diabeticorum is characterized by the abrupt appearance of asymptomatic, taut, noninflammatory bullae and
`vesicles on the feet or shins (Figure 13). Most patients with this condition have longstanding diabetes, but in some cases
`BD has been the presenting sign of diabetes mellttus. The goal of the diagnostic workup in patients presenting with bullae
`and vesicles suggestive of BD is to exclude other blistering skin disorders, and the workup should therefore include a skin
`biopsy, wound cultures, and perhaps assays for porphyrins. Healing of the lesions of BD occurs spontaneously within 2 to
`6 weeks after their appearance, and rarely leaves scarring; however, the lesions may recur in their original locations, and
`patients should be educated about this and about proper care of the lesions of BD. To alleviate discomfort and prevent
`
`secondary infection, it is recommended that the lesions of BD be aspirated and treated with topical antibiotics.38
`
`Fig. 13
`
`Bullosis diabeticorum and diabetic dermopathy. Tense, noninflammatory bullae are present within a da~ly
`
`brown-plgmented pretiblal area.
`
`Courtesy of the Department of Dermalology at the University o! Alabama, E~irmlngham, School of Modioil~e.
`
`Diabetic ulcers or mal perforans locate on pressure points and bony prominences of the foot such as the great toe,
`metatarsophalangeal joints, and heels. They occur in 15% of individuals with diabetes mellitus and lead to amputation in
`approximately 15% of these patients, Four major pathogenic factors contribute to the development of diabetic ulcers: (1)
`sensory and autonomic neuropathy; (2) abnormal biomechanlcs of the foot; (3) peripheral arterial disease (PAD); and (4)
`poor wound healing. Because sensory neuropathy in diabetic individuals results in a loss of protective sensation, foot
`trauma in persons with such neuropathy is often unrecognized and leads to ulceration. Autonomic neuropathy leads to
`anhidrosis, with the resultant dry skin being susceptible to cracks and fissures, which serve as portals of entry for bacteria.
`Poor wound healing and PAD impede the resolution of foot ulcers in diabetes and contribute to the perpetuation of
`infection. The monofilament test should be used during the routine clinical examination of a diabetic patient to evaluate for
`neuropathy. If infection is suspected, a complete blood count, erythrocyte sedimentation rate, and glucose levels should
`
`be measured and imaging studies should be done to detect involvement of deep soft tissues and bone.39
`
`Several recent studies have reviewed interventions with demonstrated efficacy for treating diabetic foot wounds.
`
`These consist of: (1) off-loading, with casts or boots designed to minimize mechanical trauma to a diabetic ulcer and
`
`therefore promote wound healing; (2) d~brldement; (3) wound dressing (ie, hydrogel); (4) the use of oral or systemic
`
`antibiotics; (5) hyperbaric oxygen therapy; and (6) revascularizatlon.40’41 Bioengineered products that act as delivery
`
`Page 8 of 14
`
`
`
`systems for growth factors and extracellular matrix are being studied for the treatment of diabetic foot ulcers recalcitrant to
`
`other treatments.4~
`
`Pernio (Chilblains)
`Pernio is an abnormal inflammatory response to cold, damp, nonfreezing conditions that occurs in predisposed
`individuals. It is frequently idiopathic, but in 20% to 40% of patients it has been associated with systemic diseases (most
`commonly lupus erythematosus, but also’cryoglobulinemia, antiphospholipid syndrome, macroglobulinemia, and
`malignancies). Pernio develops acutely as erythematous papules and plaques with or without scale on the distal legs and
`
`feet (Figure 14). It is associated with pruritus and a burning sensation, and its lesions may blister and ulcerate.43 The
`
`lesions are induced or exacerbated by cold, including postoperative cold-therapy systems used by orthopaedic
`
`surgeons.44
`
`Fig. 14
`
`Pernio, wi~h an erythematous, scaly plaque al lhe t~p of the right big toe,
`
`Courtesy of the Depaltment of Derl’natology at the University of AlabamR, Birmingham, School el Medicine.
`
`Pernio should be differentiated from frostbite, which occurs after exposure to freezing conditions. The exact
`pathogenesis of pernio remains unknown, but it has been proposed to be related to abnormal vasoconstriction,
`
`vasospasm, hyperviscosity, and autoimmunity.
`
`The most important point in the management of pernio is its prevention through the use of adequate, loose, insulating
`clothing, and of appropriate warmth in housing and in the workplace, Options for its treatment include antimalarial agents,
`
`calcium-channel blockers, mycophenolate mofetil, and high-potency topical corticosteroids.43,4s
`
`Rheumatoid Papules
`Rheumatoid papules belong to the group of palisaded neutrophilic and granulomatous dermatitis, It has been
`suggested that rheumatoid papules may represent a link between rheumatoid vasculltls and rheumatoid nodules, but the
`
`exact pathogenesis of these papules remains poorly understood.4s As much as one-thlrd of patients with such papules
`have associated rheumatic diseases (rheumatoid arthritis, seronegative nonerosive polyarthritis, systemic lupus
`erythematosus), and 6% of patients have associated hematologic disorders, including hemolytic anemia, pancytopenia,
`
`and cryoglobulinemia.47
`
`Rheumatoid papules are skin-colored or slightly red, hard papules located on the lower extremities or back and sides
`
`of the tees. Central umbilication of the papules, with crusting or perforation and ulceration, may occur. The diagnosis of
`
`rheumatoid papules should be suspected from their clinical presentation and confirmed with a skin biopsy. No specific
`
`therapy is required for this skin condition, although improvement has been reported with topical or intralesional
`
`corticosteroids, dapsone, colchiclne, and tacrotimus.48
`
`Palmoplantar Pustulosis (Psoriasis)
`Psoriasis is one of the most common dermatologic diseases, affecting as much as 3% of the wodd population.4s It is a
`
`chronic, immune-mediated disease that results from a polygenic predisposition combined with environmental triggers.
`
`Page 9 of 14
`
`
`
`Psoriatfc lesions demonstrate infiltrates of activated T-cells that are thought to elaborate cytokines responsible for
`
`keratinocyte hyperproiiferation, which results in the characteristic clintcal findings in psoriasis.5°’s’l
`
`Palmoplantar pustulosis, characterized by pustular lesions and yellow-to-brown macules, is an uncommon variant of
`psoriasis, but when present on the palms and soles is a common manifestation of psoriasis in smokers. It is also more
`common in women than in men. Local irritants, pregnancy, medications (lithium, ~-btockers, and antimalarial drugs),
`
`infections, and systemic glucocorticoid withdrawal can precipitate this form of psoriasis.$2 Clues to its diagnosis include a
`
`history or the presence of chronic plaque psoriasis (well-demarcated erythematous patches and plaques with silvery
`scales) elsewhere than onthe palms or soles and/or psoriatic involvement of the fingernails and toenails (Figure 15).
`Involvement of the nails has been re~orted in as many as 80% of patients with psoriasis, with the fingernails more often
`affected than the toenails. Psoriatic arthritis is common in the presence of nail involvement.
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`Fla. 15
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`Palmoplantar pustulosis. Pustules and yellow-to-brown macules ate distributed on the central soles
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`of both feet. Note the scaly, hyperkeratotic plaques on the forefeet and he~I8, whloh are typical of
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`chronic plaque psoriesia.
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`Courtesy of the Depadmertt of Dermatotogy al the Ueivelsity of Alabama, Sirnlingham, School of Medicine.
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`Before considering a specific treatment of psoriatic arthritis in a particular patient, it is important to exclude factors that
`trigger the condition. All patients should be instructed to avoid excess drying or irritation of the skin and to maintain
`adequate cutaneous hydration. The first line of ~’eatment of localized palmoplantar pustulosis consists of topical
`corticosterolds, often in conjunction with a tetracycline antibiotic. The use of PUVA, acitretin, methotrexate, cyclosporine,
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`and biologic agents are alternative means of treating recalcitrant palmoplantar pustulosis.~’~4
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`Reactive Arthritis
`When psoriatic lesions are accompanied by arthritis, the possibility of psoriatic arthritis or reactive arthritis should be
`considered. A history of oral ulcers, conjunctivitis, uveitis, enteritis, and/or urethritis/cervicitis points to the latter diagnosis.
`This disease Is common in young men of human leukocyte antigen (HLA)-B27 genotype. Chlamydia trachomatis is a
`major cause of reactive arthritis and may trigger the entire syndrome. Reactive arthritis and extra-articular symptoms
`usually begin 3 to 4 weeks after the onset of urethritis andtor enteritis, but may develop sooner or even precede
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`urethritis,ss The knees, ankles, and small joints of the feet are the body sites most frequently involved by reactive arthritis.
`Cutaneous manifestations arise in as much as 50% of patients. The two most common manifestations of reactive arthritis
`are keratoderma blenorrhagicum and balanitis circinata. Keratoderma blenorrhagicum is a pustular or plaque-like eruption
`that occurs in a patmoplantar distribution. Its lesions typically begin as erythematous macules or pustular-to-hemorrhagic
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`vesicles (Figure 16). With the passage of time the lesions thicken, forming a crust, and can become hyperpigmented.~s
`The manifestation of reactive arthritis known as balanitis circinata consists of erythematous plaques on the penis. The
`changes in the fingernails and toenails in reactive arthritis are similar to those in psoriasis.
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`FiB. 16
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`Reactive arthritis. Multiple pustules and hyperpigmented rnacules occurring chiefly on the planter
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`surface of the aroh and toes.
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`Page 10 of 14
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`Courtesy of the Oepmlment or Oermatology at the University of Alabama, Bh’mi~gh~.m, School of Medicine.
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`The course of reactive arthritis is marked by exacerbations and remissions. In the setting of acute or mild disease,
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`treatment is most often symptomatic and nonsurgical. Topical corticosteroids, topical calcipotriene, keratolytic agents, coal
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`tar, and phototherapy have been found beneficial for treating the cutaneous manifestations of reactive arthritis.~5
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`Palmoplantar Keratodermas
`Palmoplantar keratodermas (PPKs) represent a diverse group of hereditary and acquired disorders characterized by
`hyperkeratosis of the skin of the palms and soles. Genetically determined PPKs are characterized by inherited mutations
`in genes encoding desmosomal components, keratins, or connexins. Acquired PPKs may result from inflammatory
`diseases of the skin (eczema, psoriasis, and lichen planus), hypothyroidism, underlying malignancy, and treatment with
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`pharmacologic agents (lithium, verapamil, venlafaxine, tegafur, imatinib, glucan, capecitabine).57 The palmoplantar skin in
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`PPKs is initially red, with this being followed by the appearance of a thick, yellow hyperkeratosis that expands to involve
`the lateral aspects of the hands and feet (Figure 17). The three major patterns of distribution of hyperkeratosis in PPKs
`are: (1) diffuse, (2) focal, and (3) punctate. A diffuse PPK enco