Case: A 31 year old male opioid addict referred to Addiction Rehabilitation Center, an affiliated clinic to Addiction Research Centre for opioid abstinence therapy. He was skinny in a poor condition. He complained of impaired memory, temporary daily agitation, severe weakness, mild paresthesia, impotence and metallic taste. He was also suffered from importunate spastic abdominal cramps and colic pains which have been repeated several times during the last 6 months.
On physical examination, his blood pressure was slightly increased (135/80). Stomach was soft without any tenderness and hepatomegaly. Force of proximal and distal muscles were decreased and he was unable to stand up without any help after kneeling. Oral examination showed yellowish rotten teeth with a diffuse dark bluish discoloration of cervical tooth (Figure 1). Dermatologic inspection revealed no other pigmentation on the other parts of the body.
What are the differential diagnosis of and the proper approach to this patient?
Differential diagnosis: The main complications of the patient were recurrent spastic abdominal cramps and colic pains, fatigue and severe muscle weakness and dark bluish discoloration of periodontal tissue. The leading differential diagnoses could accordingly include (1)lead poisoning (2)hypoadrenocorticism (Addison's disease) (3)AIDS (Kaposi sarcoma) (4) bismuth stomatitis and (5) smoker’s melanosis.
A case with severe fatigue, muscle weakness, abdominal pain, and abnormal discolorations is suggestive of Addison’s disease. However, such cases are hypotensive with diffuse pigmentation on the other parts of the body rather than oral cavity (1,2). Deposition of heavy metals (lead, bismuth, mercury, silver, gold, etc.) is tended to create discolorations in oral cavity due to reaction between sulfur ions released by oral bacteria with circulating metal molecules (3). There are other causes of bluish discolorations in oral cavity, which are summarized in table 1 (2,4-18).
Table 1. Differential diagnosis of bluish discoloration of periodontal tissue
Heavy metal deposition
- Environmental and occupational exposure to lead contaminated, paints fumes, etc.
- Long term abuse of adulterated opioids and marijuana
- Drinking from leaden amphora containing wine (ancient Romans) known as colica pictonum
- Drinking from cider produced through a lead lined press known as Devonshire colic
Diffuse dark bluish discoloration on gingival sulcus, buccal mucosa and tongue. Metallic taste and burning sensation in the mouth may also be present.
Constant Inhalation of highly concentrated silver containing fumes.
Diffuse blue-gray discolorations on the skin and, to a lesser degree, on the mucosal membranes
Embedding of mercury/silver containing material into adjacent oral mucosal membrane
Single or multiple localized blue gray discolorations of variable dimensions in gingiva and alveolar mucosa. Floor of the mouth and the buccal mucosa may also be involved.
Long term treatment with gold salts (usually for rheumatoid arthritis)
Diffuse dark bluish or faint purple gingival discoloration
Increased adrenocorticotropic hormone production induces melanocyte-stimulating hormone
Multiple localized pigmentations of skin and mucosa of all over the body, weakness, nausea and vomiting, abdominal pain, constipation or diarrhea, weight loss and hypotension.
Multifocal vascular malignancy
Multiple localized brown to purple lesions of hard palate, gingiva and tongue
Increased production of melanin due to long term smoking
Diffuse brown–black discolorations of gingiva, buccal mucosa , lateral sides of tongue, palate and floor of mouth which are spontaneously resolvable after cessation of smoking
Accumulation of nevus cells in the basal epithelial layers and/or connective tissue
Single or multiple localized dark brown, gray, blue, or black of hard palate, buccal mucosa, lip, gingiva, labial mucosa, soft palate, retromolar pad and tongue
Proliferation of malignant melanocytes along the junction of the epithelial and connective tissues and within connective tissue
Single or multiple localized dark brown, gray, blue, or black of hard palate, buccal mucosa, lip, gingiva, labial mucosa, soft palate, retromolar pad and tongue. The lesions are rapidly enlarging associated with ulceration, bleeding, pain and bone destruction
Minocycline induced pigmentation
Long-term treatment with minocycline (usually for refractory acne vulgaris)
Diffuse gray bluish discolorations of the alveolar bone, which can be seen through the thin overlying oral mucosa (especially the maxillary anterior alveolar mucosa)
Physiologic (Racial) Pigmentation
Increased melanocytic activity in African, Asian and Mediterranean populations
Diffuse discoloration of marginal gingiva. Pigmentation of the buccal mucosa, hard palate, lips and tongue may also be seen
Reduction in oxygenated hemoglobin due to vitamin C deficiency
Diffuse bluish red appearance of gingiva, weakness, lethargy, bone pain, myalgia, easy bruising, petechiae, poor wound healing and emotional changes
Approach: As the first step to diagnose, complete blood count, peripheral blood smear and blood lead level (BLL) assays are recommended.
Laboratory tests of this patient revealed hypochromic microcytic anemia (Hb basophilic stippling on blood smear and a high blood lead level (840 μg/dL). This is consistent with lead poisoning. To assess the level of target organ damages, urinalysis, routine serum biochemistries and liver function tests (LFT) are required. Radiographic imaging helps to substantiate the diagnosis in doubtful cases by showing increased metaphyseal density of long bones (lead lines) (11).
In this patient, a marginal increase in serum creatinine (1.4 mg/dL) was detected. LFT and serum biochemistries were normal.
Treatment: Primarily, the exposure should be decreased. The mainstay of treatment of lead poisoning is chelation therapy. However, it is only indicated for symptomatic patients with BLL exceeding 70 µg/dL in adults and 45 µg/dL inchildren (10,11). For mild symptoms with BLL between 70 and 100 µg/dL in adults and 45-70 µg/dL in children, succimer (350 mg/m2 tid for 5 days then bid for 14 days) is the drug of choice which is administered orally. Moderate to severe cases (BLL > 100 µg/dL, encephalopathy, abdominal colic, severe artheralgia or myalgia, target organ damage) should be admitted to receive 75 mg/m2 dimercaprol (British anti-lewisite; BAL) intramuscularly every 4 hours for 5 days and 1000-1500 mg/m2 Edetate Calcium Disodium (CaNa2EDTA) via daily infusion. In case of opioid adulteration, abstinence treatment with methadone maintenance is also indicated (9,10). Supportive treatments including intravenous fluids and hemodialysis in case of renal failure may also be necessary.
Etiology: Chronic and acute lead poisoning could be the result of occupational or environmental lead exposure or rarely ingestion of lead contaminated substances (3,11). However, some cases might be the victims of lead adulteration which is a new dilemma (12-18).
Otcome: The patient received 450 mg/m2/d BAL and 1500 mg/m2/d CaNa2EDTA in divided doses for five days. He was well in further follow-ups, though he complained occasional mild abdominal discomforts.
Limitation: In classic discoloration of oral cavity due to lead toxicity, marginal gingiva is described to be involved (Burton’s sign) (11), which in this case has not been observed.
Chakera AJ, Vaidya B. Addison disease in adults: diagnosis and management. Am J Med 2010 May; 123(5):409-13.
Kauzman A, Pavone M, Blanas N, Bradley G. Pigmented lesions of the oral cavity: review, differential diagnosis, and case presentations. J Can Dent Assoc 2004 Nov; 70(10):682-3.
Pearce JM. Burton's line in lead poisoning. Eur Neurol 2007;57(2):118-9.
Charbeneau TD, Hurt WC. Gingival findings in spontaneous scurvy. A case report. J Periodontol 1983 Nov; 54(11):694-7.
Afshari R, Emadzadeh A. Short communication: case report on adulterated opium-induced severe lead toxicity. Drug Chem Toxicol 2010 Jan; 33(1):48-9.
Afshari R, Monzavi SM, Javanbakht A. Heavy metal poisoning. In: Afshari R, Monzavi SM, editors. Afshari’s Clinical Toxicology and Poisoning Emergency Care. 2nd ed. Mashhad: Mashhad University of Medical Sciences Publication; 2011. p.285-94.
Afshari R. Opioid poisoning and medical complications in Asia pacific region. In: Proceedings of the 10th Annual Congress of Asia Pacific Association of Medical Toxicology; 2011 Nov 11-14; Penang, Malaysia. p.48
Jalili M, Azizkhani R. Lead toxicity resulting from chronic ingestion of opium. West J Emerg Med 2009 Nov; 10(4):244-6.
Masoodi M, Zali MR, Ehsani-Ardakani MJ, Mohammad-Alizadeh AH, Aiassofi K, Aghazadeh R, et al. Abdominal pain due to lead-contaminated opium: a new source of inorganic lead poisoning in Iran. Arch Iran Med 2006 Jan; 9(1):72-5.
Beigmohammadi MT, Aghdashi M, Najafi A, Mojtahedzadeh M, Karvandian K. Quadriplegia due to lead-contaminated opium--case report. Middle East J Anesthesiol 2008 Oct; 19(6):1411-6.
Meybodi FA, Eslick GD, Sasani S, Abdolhoseyni M, Sazegar S, Ebrahimi F. Oral opium: an unusual cause of lead poisoning. Singapore Med J 2012 Jun; 53(6):395-7.
Verheij J, Voortman J, van Nieuwkerk CM, Jarbandhan SV, Mulder CJ, Bloemena E. Hepatic morphopathologic findings of lead poisoning in a drug addict: a case report. J Gastrointestin Liver Dis 2009 Jun; 18(2):225-7.
Busse F, Omidi L, Timper K, Leichtle A, Windgassen M, Kluge E, et al. Lead poisoning due to adulterated marijuana. N Engl J Med 2008 Apr 10; 358(15):1641-2.