Case 7 Aleodor (Doru) Andea Professor of Pathology and Dermatology - - PowerPoint PPT Presentation

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Case 7 Aleodor (Doru) Andea Professor of Pathology and Dermatology - - PowerPoint PPT Presentation

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International Academy of Pathology October, 2018 Dead sea, Jordan Case 7 Aleodor (Doru) Andea Professor of Pathology and Dermatology Director of Molecular Dermatopathology University of Michigan Ann Arbor, MI USA Clinical history

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Case 7

Aleodor (Doru) Andea

Professor of Pathology and Dermatology Director of Molecular Dermatopathology University of Michigan Ann Arbor, MI USA

International Academy of Pathology

October, 2018 Dead sea, Jordan

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  • 46-year-old African American, presents

for management of severe psoriasis

  • Refractory to treatment over last 2 years
  • Diagnosed based on clinical and

histopathologic evaluation

  • History of hepatitis C

Clinical history

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Bentley, Andea et al, J Am Acad Dermatol, 2009; 60 (3): 504-7

  • Hyperkeratotic, crusted,

erythematous plaques:

  • Hands, forearms,

lower legs, elbows and knees

  • Plantar feet
  • Nail pitting

Clinical examination

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Psoriasis refractory to therapy?

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Initiation of Zn chloride 220 mg BID

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Initiation of Zn chloride 220 mg BID Follow-up at 3 weeks

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Necrolytic acral erythema

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  • Part of the group of necrolytic erythemas:

– Acrodermatitis enteropathica (defects in zinc transport protein) – Glucagonoma syndrome (Necrolytic migratory erythema) – Necrolytic acral erythema – Hartnup disease – Aminoacidopathies (propionic and methylmalonic acidemia) – Selenium deficiency – Biotin deficiency – Glutamine synthetase deficiency (GS)

Necrolytic acral erythema

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  • First described by el Darouti et al. in 1996

with a series of 7 Egyptian patients

  • ~70-80 cases reported
  • Exclusively in patients with hepatitis C and

pathognomonic for this infection

  • Majority of cases in Africa (Egyptian) or

African-American patients

  • Zn levels usually normal

El Darouti, el Ela. Necrolytic acral erythema: a cutaneous marker of viral hepatitis C. Int J Dermatol 1996; 35:252-6 Tabibian et al. Necrolytic acral erythema as a cutaneous marker of hepatitis C: Report of two cases and review. Dig Dis Sci. 2012; 55:2735-43

Necrolytic acral erythema

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  • Acral sites: Feet>Hands
  • Dorsal aspects of feet and

hands

  • Palms, soles, nails rarely

involved

  • Non-acral involvement:

trunk, upper extremities

  • Peri-orificial areas and oral

mucosa usually spared

El Darouti, el Ela. Necrolytic acral erythema: a cutaneous marker of viral hepatitis C. Int J Dermatol 1996; 35:252-6 Abdallah et al. Necrolytic acral erythema: A cutaneous sig of hepatitis C virus infection. J Am Acad Dermatol 2005; 53:247-51

Clinical presentation

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  • Acute lesions: erythema

with vesicles and bullae

El Darouti, el Ela. Necrolytic acral erythema: a cutaneous marker of viral hepatitis C. Int J Dermatol 1996; 35:252-6 Nofal AA et al. Necrolytic acral erythema: a variant of necrolytic migratory erythema or a distinct entity? Int J of Dermatol 2005; 44:916-21 Tabibian et al. Necrolytic acral erythema as a cutaneous marker of hepatitis C: Report of two cases and review. Dig Dis Sci. 2012; 55:2735-43

Early lesion

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  • Dark red rim

Clinical presentation

Geria AN et al. Necrolytic acral erythema: A review of the literature. Cutis; 2009; 83:309-14

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Nofal AA et al. Necrolytic acral erythema: a variant of necrolytic migratory erythema or a distinct entity? Int J of Dermatol 2005; 44:916-21

Late lesion

  • Plaques with thick

scale, erosions and crusting.

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  • Parakeratosis
  • Pale keratinocytes
  • Cytoplasmic

vacuolization

  • Epidermal necrosis.

Histology -initial

El Darouti, el Ela. Necrolytic acral erythema: a cutaneous marker of viral hepatitis

  • C. Int J Dermatol 1996; 35:252-6
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Histopathology -late

  • Psoriasiform

hyperplasia

El Darouti, el Ela. Necrolytic acral erythema: a cutaneous marker of viral hepatitis C. Int J Dermatol 1996; 35:252-6

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Histopathology -late

  • Parakeratosis
  • Neutrophils in the

epidermis

  • Apoptotic cells
  • No pallor

El Darouti, el Ela. Necrolytic acral erythema: a cutaneous marker of viral hepatitis C. Int J Dermatol 1996; 35:252-6

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Pathogenesis of cutaneous lesions

  • Not clear but probably multifactorial
  • Hepatocellular dysfunction
  • Hyperglucagonemia
  • Hypoaminoacidemia
  • Hypoalbuminemia
  • Zinc deficiency: occult even with normal serum levels
  • Diabetes
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Treatment

  • Zn

– Response usually within several weeks

  • Treatment of underlying Hep C

– Leads to durable remission – Skin results even when treatment is not effective for the hepatitis

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Differential diagnosis

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Psoriasis

  • Similar clinical and pathologic

presentation

  • Does not respond to Zn and has

no association to Hep C

  • Potential for confusion:

– Nofal et al: 2 of 5 patients dx initially as psoriasis – Fielder et al: 1 patient initially dx as psoriasis on clinical and histo exam – Kapoor et al: 1 patient dx as psoriasis for 8 years clinical and histo exam, response to Zn therapy

Nofal AA et al. Necrolytic acral erythema: a variant of necrolytic migratory erythema or a distinct entity? Int J of Dermatol 2005; 44:916-21 Fielder LM et al. Necrolytic acral erythema: Case report and review of the literature Kapoor R et al. Necrolytic acral erythema. N Engl J Med. 2011; 364: 1475-6

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NAE/ Psoriasis

Kapoor R et al. Necrolytic acral erythema. N Engl J Med. 2011; 364: 1475-6

Zn therapy

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Acrodermatitis enteropathica

  • Similar histology with NAE
  • Caused by a defect in zinc

transport protein ZIP4.

  • No association with Hep C
  • Presents in infancy
  • Periorificial distribution
  • Low Zn levels
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Pityriasis Rubra Pilaris

  • No association with Hep C
  • Small follicular papules

with a central plug

  • Perifollicular erythema
  • Islands of sparing
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  • Vitamin C deficiency
  • Perifollicular

hemorrhage

  • Subungual

hemorrhages

  • Bleeding gums
  • Follicular

hyperkeratosis with corkscrew hairs

Scurvy

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  • Follicular dilatation
  • Keratin plugging
  • Perifollicular

hemorrhages

  • Chronic inflammation
  • Hemosiderin

deposition

Scurvy

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Case 8

Aleodor (Doru) Andea

Professor of Pathology and Dermatology Director of Molecular Dermatopathology University of Michigan Ann Arbor, MI USA

International Academy of Pathology

October, 2018 Dead sea, Jordan

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Clinical history

  • 26-year-old woman
  • Fever, leukocytosis, arthralgias
  • Skin rash consisting of pruritic, hyperpigmented

papules and plaques with a distinct linear and rippled morphology

  • Negative:

– ANA – anti-cyclic citrullinated protein – RF

  • Elevated: ferritin
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Woods MT, Andea AA. Am J Dermatopathol. 2011, 33:736-9

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Adult onset Still disease

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  • Still disease: Systemic-onset juvenile idiopathic

arthritis

  • Systemic inflammatory disorder
  • Unknown etiology
  • High fever
  • Polyarthralgia
  • Lymphadenopathy
  • Rash

Adult onset Still disease

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  • Major

– High fever >39C – Arthralgia – Rash – Leukocytosis

Adult onset Still disease

Yamaguchi criteria

  • Minor

– Sore throat – Lymphadenopathy/ Splenomegaly – Liver dysfunction – Negative RF and ANA

  • DX: At least 5 criteria including 2 major
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  • Additional features:
  • Elevated ferritin: marker of disease activity
  • Elevated IL-6, IL-18
  • Occasionally reactive hemophagocytic syndrome
  • Exclusion of infections, other

rheumatologic diseases or malignancy

  • Delayed dx is common

Adult onset Still disease

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  • Two groups

– Typical: evanescent “salmon-pink”, major dx criterion – Atypical: pruritic persistent eruption

Skin rash

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Yamamoto T. Cutaneous manifestations associated with adult-onset Still disease. Rheumatol Int. 2012, 32:2233-7 Lee JYY. Evanescent and persistent pruritic eruptions of adult onset Still disease: a clinical and pathologic study of 36 patients. Semin Arthritis Rheum. 2012, 42:317-26.

Evanescent rash

  • ~85% of patients
  • Salmon-pink, macular, or

maculopapular

  • Appears and disappears in

parallel with the fever episodes

  • Extremities and trunk
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  • Mild superficial

perivascular dermatitis

Evanescent rash

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  • Mild superficial

perivascular dermatitis

  • Uninvolved epidermis

Evanescent rash

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  • Lymphocytes,
  • ccasional

neutrophils

Evanescent rash

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  • Atypical rash has received little attention
  • ~65 cases reported so far

Pruritic Persistent Eruption

Yamamoto T. Cutaneous manifestations associated with adult-onset Still disease. Rheumatol Int. 2012, 32:2233-7 Lee JYY. Evanescent and persistent pruritic eruptions of adult onset Still disease: a clinical and pathologic study of 36 patients. Semin Arthritis Rheum. 2012, 42:317-26.

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  • Usually present at disease onset
  • Pruritic persistent papules or plaques
  • Trunk, neck, face, extensor extremities
  • Few morphologies

Pruritic Persistent Eruption

Yamamoto T. Cutaneous manifestations associated with adult-onset Still disease. Rheumatol Int. 2012, 32:2233-7 Lee JYY. Evanescent and persistent pruritic eruptions of adult onset Still disease: a clinical and pathologic study of 36 patients. Semin Arthritis Rheum. 2012, 42:317-26.

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  • Plaques with hyperpigmented

papules with linear/ rippled configuration

Pruritic Persistent Eruption

Wolgamot G et al. Unique histopathologic findings in a patient with adult-onset Still

  • disease. Am J Dermatopathol. 2007, 29:194-6

Lee JYY. Evanescent and persistent pruritic eruptions of adult onset Still disease: a clinical and pathologic study of 36 patients. Semin Arthritis Rheum. 2012, 42:317-26. Woods MT, Andea AA. Am J Dermatopathol. 2011, 33:736-9

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  • Urticarial papules

Pruritic Persistent Eruption

Lee JYY. Evanescent and persistent pruritic eruptions of adult onset Still disease: a clinical and pathologic study of 36 patients. Semin Arthritis

  • Rheum. 2012, 42:317-26.
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  • Lichenoid papules

Pruritic Persistent Eruption

Lee JYY. Evanescent and persistent pruritic eruptions of adult onset Still disease: a clinical and pathologic study of 36 patients. Semin Arthritis Rheum. 2012, 42:317-26.

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  • Dermatomyositis-like

Pruritic Persistent Eruption

Lee JYY. Evanescent and persistent pruritic eruptions of adult onset Still disease: a clinical and pathologic study of 36 patients. Semin Arthritis

  • Rheum. 2012, 42:317-26.
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Cho and Liao. Acta Derm Venereol. 2013, Epub ahead of print Lee JYY. Evanescent and persistent pruritic eruptions of adult onset Still disease: a clinical and pathologic study of 36 patients. Semin Arthritis Rheum. 2012, 42:317-26.

Pruritic Persistent Eruption

  • Prurigo pigmentosa-

like eruption in AOSD

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  • Lichen amiloidosis-

like

Pruritic Persistent Eruption

Lee JYY. Evanescent and persistent pruritic eruptions of adult

  • nset Still disease: a clinical and pathologic study of 36
  • patients. Semin Arthritis Rheum. 2012, 42:317-26.
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  • Superficial

perivascular dermatitis

Persistent papulosquamous rash

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  • Dyskeratotic keratinocytes,

in the upper layers of the epidermis

  • No significant spongiosis or

vacuolar-interface changes

Persistent papulosquamous rash

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  • Superficial perivascular

infiltrate

  • Lymphocytes
  • Few neutrophils
  • Variable eosinophils

Persistent papulosquamous rash

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Persistent papulosquamous rash

  • Atypical AOSD rash often confused with

dermographism or drug eruption in early reports

  • Awareness of this particular and distinctive

histology may facilitate the diagnosis

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Differential diagnosis

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Subacute cutaneous lupus erythematosus

  • Annular or papulosquamous lesions
  • Photosensitive areas: face, neck, upper

trunk, extensor surface of arms

  • Non-scarring lesions
  • May be associated with drug ingestion
  • Positive ANA
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Rheumatoid arthritis

  • Similar histology to the evanescent rash of AOSD
  • Lacks dyskeratosis
  • Positive RF and anti-cyclic citrullinated protein
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Erythema multiforme

  • Pleomorphic eruption
  • Targetoid lesions
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Dermatomyositis

  • Polymyositis
  • Skin involvement
  • 10-20% with underlying malignancy
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Dermatomyositis

  • Mild vacuolar-interface

dermatitis

  • Rare apoptotic cells
  • Sparse dermal infiltrate,
  • ften superficial
  • Abundant dermal mucin
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