Clinical stages of chronic arsenic poisoning:
(1) preclinical
(2) clinical (symptomatic or overt dermatologic changes)
(3) internal complications
(4) malignancy and severe cardiovascular disease
The preclinical stage (Stage 1) features:
(1) no clinical manifestations of arsenic poisoning
(2) positive arsenic levels in urine, blood, skin, nails and hair
Stage 2: Clinical (Dermatologic)
(1) melanokeratosis (combination of melanosis and hyperkeratotic lesions), especially affecting the palms and soles
(2) diffuse melanosis
(3) spotted melanosis (raindrop pigmentation)
(4) leucomelanosis (pigmented and depigmented spots on the trunk and/or legs)
(5) keratosis
(6) pigmentation of the buccal mucosa
(7) nonpitting edema
(8) conjunctival congestion (with reddening of the eyes)
Stage 3: Internal complications
(1) asthmatic bronchitis
(2) splenomegaly
(3) hepatomegaly with noncirrhotic portal fibrosis
(4) anemia with weakness
(5) myalgia and myopathy
(6) chronic laryngitis
(7) adrenal gland hypofunction
(8) peripheral neuropathy
(9) CNS toxicity
Stage 4: Malignancy or severe vascular disease
(1) arteriosclerosis obliterans with gangrene
(2) Bowen's disease of the skin
(3) squamous cell carcinoma of the skin
(4) carcinomas of internal viscera (lung, urinary bladder, liver, uterus)