title: Cutaneous Hyperpigmentation in Megaloblastic Anemia: a Five Year Retrospective Review.
abstract: BACKGROUND
  Cutaneous hyperpigmentation is an often overlooked clinical sign in megaloblastic anemia (MA) which has been sporadically reported in the literature.
  
  
  METHODS
  We describe the bone marrow (BM) changes and clinicolaboratory characteristics of 25 of 198 adult cases (>16 years) with cutaneous hyperpigmentation who underwent BM evaluation for cytopenia (s).
  
  
  RESULTS
  Twenty-one of 25 cases (84%) had MA, while MA without hyperpigmentation occurred only in 12 of remainder 173 cases (P<0.001). Knuckle pad hyperpigmentation (KP) was noted in 16 (64%) cases; whereas 9 (36%) had diffuse brownish black discoloration (DP) of the palms and/or soles. Eighteen of 25 (72%) cases had pancytopenia (13 with KP) and 7 of 25 (28%) had bicytopenia (3 with KP). In addition, five cases (20%) presented with pyrexia. Of the 17 cases where data available, eleven were B12 deficient [<190 pg/ml; eight had severe deficiency (<100 pg/ml); ref.; 190-800pg/ml], while 4 had pure folate deficiency (< 4.0 ng/ml; ref.; 4-20ng/ml); and remainder 2 had combined B12 and folate deficiency. Compared to those with diffuse pigmentation; KP group had lower Hb (69.6 ± 24.2 vs. 86.3 ± 33.9 g/L), higher MCV (106.1 ±12.6 vs. 99.2 ± 7.6 fL), lower platelet count (50.9 ± 29.3 vs. 69.6 ± 36.5 × 10(9)/L), and lower median B12 [100.0 (30.0 - 822.0) vs. 316.0 (142.0 - 1617.3) pg/ml] (P>0.05). In six cases where follow-up data were available, there was a significant reversal of hyperpigmentation at 12 weeks following parenteral cobalamin therapy. In all five cases with pyrexia, fever subsided after 24 to 72 hours following administration of parenteral cobalamin therapy.
  
  
  CONCLUSIONS
  Cutaneous hyperpigmentation and cytopenia (s) are strongly associated with megaloblastic anemia. Knuckle pad hyperpigmentation is much more frequent than diffuse pigmentation of the palms and/or soles in such patents. A nonsignificant trend towards a greater degree of MA was found in cases with pigmentation of the knuckles.
authors.affiliation: Department of Pathology, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: Somanath
authors.initials: S
authors.lastname: Padhi
authors.affiliation: Department of Biochemistry, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: RajLaxmi
authors.initials: R
authors.lastname: Sarangi
authors.affiliation: Department of Pathology, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Ramdas
authors.affiliation: Department of Biostatistics, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: Kandasamy
authors.initials: K
authors.lastname: Ravichandran
authors.affiliation: Department of Pathology, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: Renu G'Boy
authors.initials: RG
authors.lastname: Varghese
authors.affiliation: Department of Gastroenterology, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: Thomas
authors.initials: T
authors.lastname: Alexander
authors.affiliation: Department of Gastroenterology, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: George
authors.initials: G
authors.lastname: Kurian
authors.affiliation: Department of General Medicine, Pondicherry Institute of Medical Sciences, Puducherry, India.
authors.forename: Sudhagar
authors.initials: S
authors.lastname: Mookkappan