Cutaneous Hyperpigmentation in Megaloblastic Anemia: A Five Year Retrospective Review.

Abstract

BackgroundCutaneous hyperpigmentation is an often overlooked clinical sign in megaloblastic anemia (MA) which has been sporadically reported in the literature.MethodsWe 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).ResultsTwenty-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 × 109/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.ConclusionCutaneous 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.

The association between low serum Vitamin B12 levels and hyperpigmentation on patients who use Isotretinonin

“…The hyperpigmentation in the presence of Vit-B12 deficiency is due to decreased glutathione levels and the over-activation of tyrosinase and/or related proteins caused by defective DNA synthesis. It has also been expressed that hyperhomocysteinemia leads to cysteine accumulation which increases the amount of melanin and leads to erroneous melanin production in keratinocytes from melanocytes[23][24][25]. In our study, a decrease in vit-B12levels in the 6-month O-ISO use may lead to abnormal pigment metabolism.…”

Acquired Vitamin B12 Deficiency: Cutaneous Hyperpigmentation and Hepato-Splenomegaly in Megaloblastic Anaemia / Pancytopenia Reported in a 15-Month-Old Boy

“…In six cases where follow-up data were available, there was a significant reversal of hyperpigmentation at 12 weeks following parenteral cobalamin therapy. Whereas fever in all five cases was subsided after 24 to 72 hours following administration of parenteral Vitamin B12 therapy [4] .…”

Cutaneous hyperpigmentation as a diagnostic marker of vitamin B12 deficiency: a case report

“…It may be the first, and sometimes the only sign of VB12D. 5,[11][12][13][14][15] The index patient had pernicious anaemia and the welldocumented pattern of acral hyperpigmentation was evident right from the onset of the disease, nonetheless, even in the presence of anaemia and myriad mucocutaneous pointers, VB12D was not considered. This may be due to the absence of the overt neurological features of sub-acute combined degeneration of the spinal cord, a late manifestation of VB12D often erroneously considered to be requisite to its diagnosis.…”