Skin nontumor
Dermal collagen and elastic tissue alterations, and cutaneous deposits
Ochronosis


Minor changes: 25 November 2020

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PubMed Search: Ochronosis[title] free full text [sb]

Chico J. Collie, M.B.B.S.
Jonathan D. Ho, M.B.B.S., D.Sc.
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Cite this page: Collie CJ, Ho JD. Ochronosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skinnontumorochronosis.html. Accessed January 18th, 2021.
Definition / general
  • Disorders characterized by blue-gray to black pigmentation due to deposition of ochre colored pigment in connective tissues
  • 2 main forms: alkaptonuria / endogenous ochronosis (homogentisate 1,2 dioxygenase deficiency) and exogenous ochronosis (overuse of topical hydroquinone and other medicaments)
Essential features
  • Deposition disorder characterized by deposition of homogentisic acid in connective tissue
  • May result from an inborn error of metabolism (alkaptonuria) or from overuse of topical hydroquinone or other phenol containing medications (exogenous ochronosis)
  • Alkaptonuria presents with hyperpigmentation, arthropathies, kidney disease and heart disease
  • Exogenous ochronosis patients primarily present with hyperpigmentation involving the face, neck or upper limbs
  • Classical histologic findings in the skin include formation of banana shaped, yellow-brown deposits and heavy elastosis in the superficial dermis
ICD coding
  • Alkaptonuria
    • ICD-10: E70.29 - Other disorders of tyrosine metabolism, ochronosis
    • ICD-11: 5C50.10 - Alkaptonuria, ochronosis
  • Exogenous ochronosis
    • ICD-10: L81.9 - Disorder of pigmentation, unspecified
    • ICD-11: ED6Y - Other specified disorders of skin pigmentation, exogenous ochronosis
Epidemiology
Sites
  • Alkaptonuria: skin (ear, face, acral surfaces and axillae), sclera, bone cartilage, kidney and cardiac valves
  • Exogenous ochronosis: skin of the malar areas, temples, lower cheeks, neck, forearms and hands
Pathophysiology
  • Alkaptonuria
    • Inborn error of tyrosine metabolism secondary to autosomal recessive loss of function mutations in HGD / HGO (Nat Genet 1996;14:19)
    • Resultant deficiency of homogentisate 1,2 dioxygenase leads to accumulation of homogentisic acid and eventual deposition in collagen rich tissue (Calcif Tissue Int 2017;101:50)
    • Long term deposition leads to degenerative arthritis, cardiac valvulopathy, renal disease and oculocutaneous pigmentation (N Engl J Med 2002;347:2111)
  • Exogenous ochronosis
Etiology
Clinical features
Diagnosis
Laboratory
Radiology description
  • Xray findings in alkaptonuric arthropathy include joint space narrowing, osteophyte formation, joint space calcification and reactive sclerosis of articular surfaces (Radiol Med 2005;110:349)
Radiology images

Images hosted on other servers:

Preoperative Xrays of right knee

MRI of right knee

Prognostic factors
  • Alkaptonuria
  • Exogenous ochronosis
    • Late diagnosis and extensive hyperpigmentation at time of diagnosis connote poor prognosis
Case reports
Treatment
Clinical images

Contributed by Jonathan D. Ho, M.B.B.S., D.Sc.

Forearm macules



Images hosted on other servers:

Pigmented knee cartilage

Pigmented papules

Facial pigmentation

Microscopic (histologic) description
  • Features of ochronosis are similar in both alkaptonuria and exogenous ochronosis
  • Early changes include homogenization of collagen and degenerating elastotic fibers (Am J Dermatopathol 2014;36:989, Am J Dermatopathol 2019 Nov 12 [Epub ahead of print])
  • Yellow-brown, banana shaped, sickled or round ochronotic bodies deposit in the connective tissue
  • Occasional bodies may be seen in direct continuity with collagen or elastic fibers (Am J Dermatopathol 2019 Nov 12 [Epub ahead of print])
  • Exogenous ochronosis
    • Extensive solar elastosis-like change is noted in an interfollicular distribution
    • Decreased basal keratinocyte pigmentation
    • Occasionally, ochronotic bodies are seen in association with colloid milium and are designated pigmented colloid milium (J Dermatol Case Rep 2015;9:42)
    • Granulomatous reaction has also been reported (J Cutan Pathol 1990;17:236)
  • Similar ochronotic bodies are seen in the connective tissues of cardiac, scleral and bony tissue when involved
Microscopic (histologic) images

Contributed by Jonathan D. Ho, M.B.B.S., D.Sc.

Ochronotic bodies

Ochronotic bodies embedded in elastosis

Ochronotic bodies staining with Verhoeff van Gieson

Pigmented, ochronosis associated colloid milium

Swollen collagen bundles

Electron microscopy description
  • Electron dense material within elastic fibers
  • Degeneration of elastic fibers with fragmentation, clearing and a moth eaten appearance
  • Reference: Arch Dermatol 2010;146:1021
Electron microscopy images

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Exogenous ochronosis

Molecular / cytogenetics description
Sample pathology report
  • Right cheek, punch biopsy:
    • Ochronosis (see comment)
    • Comment: The specimen exhibits extensive elastosis in an interfollicular distribution and scattered yellow-brown, banana shaped deposits in the superficial dermis in keeping with exogenous ochronosis.
Differential diagnosis
  • Melasma:
    • Increased keratinocyte melanization, which may involve all layers of the epidermis
    • Variable papillary dermal melanophages
    • Solar elastosis
    • Telangiectasia
    • Increased mast cells
  • Acquired bilateral nevus of Ota-like macules (Hori nevus):
    • Scattered dendritic melanocytes in the superficial dermis
    • Cells typically heavily pigmented and express melanocyte markers
  • Argyria:
    • Fine, black granules deposited on the basement membrane of blood vessels and skin adnexa
  • Lichen planus pigmentosus:
    • Subtle interface dermatitis (active lesion)
    • Focal band-like lymphocytic infiltrate (active lesion)
    • Band-like or perivascular heavily pigmented melanophages (active and burnt out lesions)
  • Facial acanthosis nigricans:
    • Hyperkeratosis
    • Papillomatosis
    • Only subtle increase in basal keratinocyte pigmentation
Board review style question #1

A 40 year old Afro-Caribbean woman with a history of long term use of skin lightening products presents with an asymptomatic hyperpigmented eruption involving the face. A punch biopsy reveals yellow-brown, banana shaped deposits in the superficial dermis. What is the most likely diagnosis?

  1. Acanthosis nigricans
  2. Argyria
  3. Exogenous ochronosis
  4. Lichen planus pigmentosus
  5. Melasma
Board review style answer #1
C. Exogenous ochronosis

Comment Here

Reference: Ochronosis
Board review style question #2
A 60 year old man presents for hip replacement. On preoperative evaluation, black discoloration of the sclera and ear cartilage are noted and a diagnosis of alkaptonuria is entertained. What enzyme is deficient in patients with alkaptonuria?

  1. Fumarylacetoacetate hydrolase
  2. Homogentisate 1,2 dioxygenase
  3. Tyrosinase
  4. Tyrosine aminotransferase
  5. 4-hydroxyphenylpyruvate dioxygenase
Board review style answer #2
B. Homogentisate 1,2 dioxygenase

Comment Here

Reference: Ochronosis
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