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

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

3. I have no financial disclosures.

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

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

6. 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

7. Pustule
Pustular Psoriasis

8. Vesicle
Herpes simplex

9. Bulla
Fluid filled lesion more than 0.05 cm in size.

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

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

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

13. Secondary Lesions Crust Erosions and ulcers Excoriations Fissures
Scars
Lichenification
Atrophy

14. Creating a Framework
Question #2
Is there scale?

15. 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

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

17. Configuration Annular Arcuate Geographic Discrete Confluent
Serpiginous
Linear
Reticulated

18. Creating a Framework
Question #4
What is the color?

19. Color
Pink
Violet
Orange
Blue
Green
Yellow
Black
Brown

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

21. 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

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

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

24. Herpes Simplex
A: Contact Dermatitis B. Herpes Simplex

25. 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!!

29. Herpes Simplex Virus Eczema Herpeticum

30. Herpes Simplex Virus Eczema Herpeticum

31. 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.

32. 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

33. Erythema Multiforme

35. 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

36. 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

37. Stevens-Johnson Syndrome

38. Stevens-Johnson Syndrome

39. Stevens-Johnson Syndrome

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

41. 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

42. 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.

43. 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.

44. 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.

45. 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

46. 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

47. 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

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

49. “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!”

51. Tinea Pedis

52. Tinea Cruris-Don’t use steroids!

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

55. Scabies

56. 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).

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

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

59. Scabies burrow

60. Crusted Scabies

61. 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.

62. Verruca Vulgaris Liquid Nitrogen Candida Antigen IL Bleomycin
Curretage and cautery

63. Condyloma

64. 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 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.

65. 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 Jul-Aug;18(4):

66. 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 Jul-Aug;18(4):

67. 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 Jul-Aug;18(4): Review.

68. Molluscum Contagiosum

69. 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

70. Auto-Immunity

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

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

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

74. 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

75. Dermatomyositis

76. 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.

77. 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

78. 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.

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

80. 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.

81. 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

82. Vasculitis

83. 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.

84. 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.

85. 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.

87. Fluid Overload

88. Stasis Dermatitis

89. Stasis Dermatitis

90. 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.

91. 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)

92. 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

93. 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

94. 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

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

96. Diabetes

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

98. 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)

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

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

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

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