Dermatologic Manifestations of Chronic Disease Shelbi Hayes. M.D. Saints Dermatology October, 26 2012

I. Creating a Framework for Evaluating Skin Lesions II. Application of the framework to the most common manifestations of chronic disease

I have no financial disclosures.

Is this a primary or secondary lesion? Creating a Framework Question #1 Is this a primary or secondary lesion?

Macule Patch Papule Plaque Macule A circumscribed, flat discoloration that may be brown, blue, red, or hypopigmented

Pustule Nodule Vesicle Bulla Pustule Nodule Nodule A circumscribed, elevated, solid lesion more than 0.5 cm in diameter; a large nodule is referred to as a tumor. Nodules are dermal or subdermal lesions

Pustule Pustular Psoriasis

Vesicle Herpes simplex

Bulla Fluid filled lesion more than 0.05 cm in size.

Wheals Wheals are elevated, blanched lesions which result from increased tissue fluid dispersed in the dermis.

Wheals Wheals are elevated, blanched lesions which result from increased tissue fluid dispersed in the dermis.

Morphologic categories Macular-Patch Papular Papulosquamous (scaly papules) Nodular Pustular Vesicular-bullous Urticarial Petechial Telangiectasia Burrow Poikiloderma Hyperkeratotic/scale Atrophic

Secondary Lesions Crust Erosions and ulcers Excoriations Fissures Scars Lichenification Atrophy

Creating a Framework Question #2 Is there scale?

Scale or No Scale? Scale indicates the disease process involves the epidermis. Lack of scale indicated the disease process affects the dermis or subcutaneous fat. Exception: Tinea Incognito, Early Vesiculobullous Lesions

What is the configuration? Creating a Framework Question #3 What is the configuration?

Configuration Annular Arcuate Geographic Discrete Confluent Serpiginous Linear Reticulated

Creating a Framework Question #4 What is the color?

Color Pink Violet Orange Blue Green Yellow Black Brown

Color Top Row: Blue-amioderone Yellow-eruptive xanthoma; Bottom row: grey-erythema dyschomium perstans Purple-lichen planus

Color Pink—Pityriasis rosea Violet—Lichen planus Orange—Juvenile xanthogranuloma Blue—Amiodarone skin pigmentation Green—Pseudomonas Yellow—Xanthomas Black—Eschar Brown—Café au lait spots

What is the distribution? Creating a Framework Question #5 What is the distribution?

Immunosuppression Due to HIV/AIDS or medication, ie transplant patients

Herpes Simplex A: Contact Dermatitis B. Herpes Simplex

Herpes Simplex Caused by HSV-1 and HSV-2 Infections occurs at the primary site, transported via neurons to dorsal root ganglion where latency is established Pain, tenderness or tingling occur often before reactivation. Grouped vesicles on erythematous base, however you may not see the primary lesion when the patient presents!!

Herpes Simplex Virus Eczema Herpeticum

Herpes Simplex Virus Eczema Herpeticum

Herpes Zoster Slide #20, "2320-Varicella and Herpes Zoster concomitantly" from Set #23 Subtitle: Viral Infections Disease: VARICELLA Disease 2: ZOSTER Age: Child Race: Caucasian Notes: This 3-year-old white boy had widespread VARICELLA and facial ZOSTER at the same time. He was treated in the hospital with I.V. acyclovir and made a rapid recovery.

EM-SJS-TEN Spectrum of epidermal damage +/- mucosal involvement EM minor = no mucous membrane EM in kids usually secondary to HSV, drugs in adults SJS-TEN constitute one of the few derm emergencies Treat in burn unit, frozen section of bx to check for necrosis, little inflammation Fluids, infection prophylaxis, consult ophtho and uro as indicated

Erythema Multiforme

Erythema Multiforme Major Also thought to be a hypersensitivity reaction As with EM minor, but with involvement of ≥2 mucosal surfaces (precedes rash by 1-2 days) Pronounced constitutional symptoms common EM Major is also thought to be a hypersensitivity reaction The skin findings are similar to EM minor, but there is involvement of 2 or more mucosal surfaces- mucosal involvement generally precedes the rash by 1-2 days Pronounced constitutional symptoms common This little girl has tagret lesions evident as well as conjunctival and oral mucosal involvment

Stevens-Johnson Syndrome Is SJS separate entity from EM major? Some feel SJS is a distinct entity as the rash is more erythematous and less acral than EM major EM major is more commonly triggered by infections and SJS by drugs. Again, it is unclear whether Stevens Johnson Syndrome is a distict disease entity from EM major – most of the clinical literature groups the two entities together but some make the distinction that SJS is more erythematous and less acral than EM major and the SJS is triggered more commonly by drugs and EM major by infection

Stevens-Johnson Syndrome

Stevens-Johnson Syndrome

Stevens-Johnson Syndrome

Toxic Epidermal Necrolysis Nikolski’s Sign = separation of the epidermis from the dermis by rubbing skin between the lesions

Toxic Epidermal Necrolysis (TEN) A life-threatening, exfoliating disease of the skin and mucous membranes Hallmark is full-thickness necrosis of the epidermis with separation at the dermoepidermal junction. TEN isa life-threatening, exfoliating disease of the skin and mucous membranes Its hallmark is full-thickness necrosis of the epidermis with separation at the dermoepidermal junction

SJS vs TEN Some use %BSA to define with: <10% = SJS >30% = TEN Histologically SJS has a much higher density cell infiltrate (T-lymphocytes) vs TEN (low density macrophages and dendrocytes) As for distinguishing SJS from TEN, there are some histological distinctions, but a more convenient way of classifying them is by the %BSA involved. The convention is to refer to patients with < 10%BSA as having SJS and for those with >30% BSA as TEN Clearly there’s a grey zone in between.

TEN - Pathogenesis Majority of cases are likely adverse drug reactions (foreign antigen response). Mean time from drug to onset = 13.6 days Higher risk drugs NSAIDS [38%] Antibiotics [36%] (sulfonamides) Anticonvulsants [24%] (phenobarb, lamotrigene) Corticosteroids [14%] Majority of cases are likely adverse drug reactions (foreign antigen response) Mean time from drug to onset = 13.6 days Higher risk drugs NSAIDS [38%] Antibiotics [36%] (sulfonamides) Anticonvulsants [24%] (phenobarb, lamotrigene) Corticosteroids [14%] As you can see, these are frequently used drugs in the pediatric population. Lamotrigene, a commonly used anticonvulsant in children with difficult to manage seizures has recently been linked to TEN - with the risk estimated to be as high as 1 in 50 children – those co-medicated with valproate are at highest risk.

Use Trimethoprim-Sulfamethoxazole Judiciously. Up to 17% of patients can have an adverse cutaneous reaction. Occurs within the first 3 weeks. Warn Patients to alert you immediately. Do not prescribe if the patient has a family history of sulfa allergy.

TEN - Clinical Features Initial symptoms (1-3 days) Fever (100%) Conjuctivitis (32%) Pharyngitis (25%) Pruritis (28%) Headache, myalgias, arthralgias, vomiting, and diarrhea may occur The Initial symptoms of TEN evolve over 1-3 days. They include: Fever (100%) Conjuctivitis (32%) Pharyngitis (25%) Pruritis (28%) Headache, myalgias, arthralgias, vomiting, and diarrhea may occur

TEN - Clinical Features: Mucosal Involvement Erosive mucosal lesions (1-3 days before skin eruption) occur in 97% Oral (93%) Ocular (78%) Genital (63%) Anal Erosive mucosal lesions occur in 97%of patients and typically precede the skin eruption by 1-3 days The lesions are seen most commonly in the mouth, followed by the eyes and genital tract

TEN - Clinical Features: Skin Eruption Burning / painful skin rash Usually begins on face / upper trunk Begins as one of: Diffuse erythema Irregular bullae Poorly defined dusky or erythematous macules Scalp usually spared The rash of TEN usually begins on face and upper trunk and is reported to be burning and painful It may appear in one of 3 patterns: Diffuse erythema Irregular bullae Poorly defined dusky or erythematous macules Scalp usually spared

Multisystem Involvement GI - Mucosal sloughing in esophagus (dysphagia, GI bleeding) Resp - Tracheal/bronchial erosions (Respiratory decompensation) Renal – Glomerulonephritis Profound fluid and electrolyte disturbances

“If it is scaly, SCRAPE it!” Dermatophytes Named for area involved: tinea capitis, corporis, manum, facei, pedis, cruris, etc. If there is scale, do KOH exam. Words of a famous dermatologist: “If it is scaly, SCRAPE it!”

Tinea Pedis

Tinea Cruris-Don’t use steroids!

Tinea Incognito Corticosteroids mask the typical annular configuration of tinea corporis.

Scabies

Scabies Caused by Sarcoptes scabiei Pregnant female mite burrows in the stratum corneum, lays eggs about 2-3 per day. Eggs hatch after about a week. See burrows, papules, vesicles. In immunocompromised and elderly, can be crusted and hyperkeratotic (Norwegian also called Crusted Scabies).

Scabies Scabies love babies! Scabies love warm, occluded places: axilla, webspaces, groin, head of penis

Distribution Pruritic, erythematous papules on the head of the penis=scabies until proven otherwise.

Scabies burrow

Crusted Scabies

Verruca Vulgaris Amy Paller et al.     Amy Paller et al. 61 children with recalcitrant warts were treated with squaric acid. They used a concentration of 2% in acetone as the sensitizing dose, applied by the physician. Then, after 1 or 2 weeks, the parent was taught to apply the elicitation dose of squaric acid 0.2% to the warts at home. Initially the dose was applied two to three times a week, increased by one application per week until the material was being applied once daily. If there was no response by week 6, the dose was increased to 0.5%. Patients were evaluated at 6- to 8-week intervals, and 58% showed complete resolution of warts. Topical immunotherapy was initially described with dinitrochlorobenzene (DNCB),[18] [21] which is a potent topical sensitizing agent that was also found to be mutagenic by the Ames test. Many reports have lauded the efficacy of this immunotherapeutic agent for treating both warts[19] [22] and alopecia areata,[23] [26] but the mutagenic potential has limited its clinical usefulness. Two other topical sensitizing agents have been suggested for wart immunotherapy: diphencyclopropenone (DCP)[27] [31] and squaric acid,[32] [33] which is available both as squaric acid dibutylester (SADBE) and squaric acid ethylester. Although efficacious in wart immunotherapy as well as in alopecia areata, local side effects with DCP have been reported to be more frequent and often severe,[30] and the product is photoinactivated with minimal light exposure.[34] There has also been a report of 3 patients with erythema multiforme–like eruptions associated with DCP.[35] SADBE, which forms a stable solution in acetone,[36] is a highly potent topical sensitizer used in crystal refraction studies and for the formation of industrial dyes. Two studies have evaluated weekly or biweekly in-office application of SADBE to warts,[32] and several studies have demonstrated the long-term safety of SADBE usage in children. [37] [41] Because of the unrealistic expectation that children will come in weekly or biweekly for treatment of warts, this study evaluated at-home application of SADBE in children with warts.

Verruca Vulgaris Liquid Nitrogen Candida Antigen IL Bleomycin Curretage and cautery

Condyloma

Treatment for CA Avoid liquid nitrogen Apply Podophyllin in the office and Rx imiquimod at home. S, Pniewski T, Malejczyk M, Jablonska S. Imiquimod is highly effective for extensive, hyperproliferative condyloma in children. Pediatr Dermatol. 2003 Sep-Oct;20(5):440-2. Sharquie KE, Al-Waiz MM, Al-Nuaimy AA. Condylomata acuminata in infants and young children. Topical podophyllin an effective therapy.

Notify CPS? CPS should be notified of concerns of possible sexual abuse when ano-genital warts are diagnosed in any child older than 3 years. It also is important for CPS to be educated by the reporting medical provider of other possible nonsexual modes of transmission for the ano-genital warts. Hornor G.Ano-genital warts in children: Sexual abuse or not? J Pediatr Health Care. 2004 Jul-Aug;18(4):165-70.

Notify CPS? For children younger than 3 years, CPS should be notified if other risk factors are noted during assessment, such as an abnormal genital examination, the presence of another sexually transmitted disease, or psychosocial information that warrants investigation Hornor G.Ano-genital warts in children: Sexual abuse or not? J Pediatr Health Care. 2004 Jul-Aug;18(4):165-70.

Recommendations Child 2 years or younger Child 3 years or older No report to child protective services needed unless one of the following is present: Abnormality noted on ano-genital examination that is of concern for sexual abuse Another sexually transmitted disease Psychosocial/behavioral issue that is of concern for sexual abuse Parental concern of sexual abuse that warrants investigation Child 3 years or older Report concerns of possible sexual abuse to child protective services Nonleading interview of child regarding sexual abuse concerns (should be completed by a trained forensic interviewer) Hornor G.Ano-genital warts in children: Sexual abuse or not? J Pediatr Health Care. 2004 Jul-Aug;18(4):165-70. Review.

Molluscum Contagiosum

Molluscum Contagiosum Caused by pox virus Characteristic umbillicated papules, molluscum bodies on biopsy May be an STD in adults – suprapubic and genital lesions Giant molluscum in AIDS pts, ddx in this pop. includes crypto and other fungal infections Tx includes cryo, curettage, cantharidin, imiquimod or nothing – they will spontaneously resolve

Auto-Immunity

Lupus ACLE Malar or butterfly rash. Most commonly associated with SLE, almost all patients have SLE. Transit, sun exacerbated, non scarring.

Lupus SCLE 10-15% will or have SLE. Exacerbated by sun, non-scarring

Lupus DLE Least associated with SLE (5-10%). Most chronic of the 3, exacerbated by the sun, scarring (including alopecia).

Lupus Must evaluate all forms of cutaneous lupus for systemic lupus ANA, anti-ds DNA, anti-Ro (especially with SCLE), complement levels, UA Review current medications Treatment is a combination of system steroids and steroid sparing agents (especially Plaquenil), mild cases may be treated with only topical steroids

Dermatomyositis

Slide #16, "0616-Dermatomyositis" from Set #6 Disease: Dermatomyositis Age: Adult (18-60) Notes: This 44-year-old woman shows the typical erythematous eruption of dermatomyositis over the upper back ("shawl sign"). She also had similar involvement on her upper anterior chest, and over the knees and elbows --- the classic distribution of the rash of dermatomyositis. She was markedly pruritic and did not have evidence of muscle involvement. Malignancy workup was negative.

Slide #31, "1431-Dermatomyositis Gottron's Papules" from Set #14 Class: Inflammatory and Metabolic Disorders Disease: Immunologic Connective Tissue Disorders Disease 2: Cutaneous Manifestations of Systemic Disease Age: Adult (18-60) Race: Caucasian Image Type: Clinical Photograph

Dermatomyositis Scalp involvement is relatively common and manifests as an erythematous to violaceous, scaly dermatitis. Clinical distinction from seborrheic dermatitis or psoriasis is occasionally difficult. Nonscarring alopecia may occur and often follows a flare of systemic disease.

Dermatomyositis Heliotrope rash Gottron papules Malar erythema Poikiloderma in a photosensitive distribution Violaceous erythema on the extensor surfaces, Periungual and cuticular changes

Dermatomyositis In 40% of patients, the skin disease may be the sole manifestation at the onset. Muscle disease may occur concurrently, precede, or follow the skin disease by weeks to years. The disease is often intensely pruritic. Systemic manifestations may occur. ROS: arthralgias, arthritis, dyspnea, dysphagia, arrhythmias, and dysphonia.

Dermatomyositis Malignancy is possible in any patient with DM, but it is much more common in adults older than 60 years. All adults must be screened. Children with DM may have an insidious onset that hides the true diagnosis until the dermatologic disease is clearly observed

Vasculitis

Vasculitis Characterized by size of vessel. Most common cutaneous disease involves small vessels, i.e. leukocytoclastic vasculitis (“Palpable Purpura”). Medium sized vessel disease includes PAN, Wegeners, and Churg-Strauss.

Vasculitis Acronym for DDx of LCV: Mt Sinai Hospital Center Meds/Malig Strep/Serum sickness Henoch Schonlein/HCV Connective tissue disease/Cryoglobulinemia HSP usually <10 y.o. but can be adults, subsequent to URI. IgA around blood vessels Watch renal function.

Vasculitis Treatment 1. Identify and eliminate underlying cause. 2. If arthralgias present consider starting NSAIDS. 3. Colchicine, dapsone, and immunosuppressive agents may be used if vasculitis is chronic.

Fluid Overload

Stasis Dermatitis

Stasis Dermatitis

Stasis Dermatitis Typically affects middle-aged and elderly patients. Occurs on the lower extremities in patients with chronic venous insufficiency and venous hypertension. Prevalence is 6-7% in patients older than 50. This finding makes stasis dermatitis twice as prevalent as psoriasis and only slightly less prevalent than seborrheic dermatitis.

Stasis Dermatitis Insidious onset of pruritus affecting one or both lower extremities. Reddish-brown skin discoloration is an early sign and may precede the onset of symptoms. The medial ankle is most frequently involved, with symptoms progressing to involve the foot and/or the calf. H.O. dependent leg edema H.O. factors that worsen peripheral edema (CHF, HTN with diastolic dysfunction)

Stasis Dermatitis Treatment is two-fold: Relief of symptoms Treatment of underlying venous insufficiency For pruritus and eczematous component: Class IV or V topical corticosteroids and emollients (AVOID NEOMYCIN) Daily use of support stockings

Id Reaction Autosensitzation dermatitis Most often pts with stasis and contact dermatitis Follows primary lesions by days to weeks Treatment includes treatment of inciting event, topical and IM steroid

Pruritus Extremely common in patients with chronic renal failure Much more common in patients on renal dialysis vs peritoneal dialysis Independent marker for mortality for patients of hemodialysis

Pruritus Antihistamines of some help Doxepin Topical capsaicin cream or Sarna lotion Efficient hemodialysis UVB

Diabetes

Eruptive Xanthomas Patients with poorly controlled glucose and elevated triglycerides Resolution with tight glucose control

Necrobiosis Lipoidica Diabeticorum 0.03% of patients with diabetes Resolution or progression is not related to glucose control Very difficult to treat Topical or IL steroid Topical tacrolimus Surgical excision (often recur)

Acanthosis Nigricans Associated with obesity and insulin resistance Improved with weight loss and glucose control Treatment includes topical retinoids and salicylic acid

Diabetic Bullae Appears on background of normal skin Resolves spontaneously Culture fluid for secondary infection of it appears cloudy

Diabetic Dermopathy Patients with poorly controlled diabetes Correlates with vacsular damage secondary to diabetes No treatment needed thought to improve with improved glucose control

“More is missed by not looking than by not knowing” M. McKay, M.D.