Key Clinical Message:
There are various causes of cutaneous green discoloration including
granulocytic sarcoma, poisoning, acute pancreatitis, eccrine
chromhidrosis and chronic liver disease. To our knowledge, we report the
first case of acral green pigmentation:
Introduction:
Primary sclerosis cholangitis (PSC) is an autoimmune disease of the
liver characterized by a progressive course
of cholestasis with
inflammation and fibrosis of the intrahepatic and extrahepatic bile
ducts that can associated to hyperbilirubinemia in complicated or
advanced stage. The spontaneous appearance of green discoloration of the
hair, skin, and nails is unusual (1,2). There are various causes of
cutaneous green discoloration. Causes are multiple include granulocytic
sarcoma, poisoning, acute pancreatitis, eccrine chromhidrosis and
chronic liver disease.
Case report
A 33-year-old woman was examined for abnormal bilateral pigmentation on
palms, which lasted two weeks. She was a housewife and she had
decompensated cirrhosis complicating PSC as underlying diseases. She was
hospitalized a month before for severe iron deficiency anemia with
Hemoglobin level at 5.5 g per dl without externalized bleeding. She had
a blood transfusion with a non-hemolytic febrile reaction. This episode
was jugulated after stopping transfusion. She had intravenous iron
replacement cure. On clinical examination, green desquamative papules
were observed on the two palms (Fig.1) and levels of total (34.4 mg/dl)
and direct (17 mg/dl) bilirubin were elevated. No specimen for
histological research was done because lesions were already
desquamative. Bacterial samples were done without any sign of fungic or
bacterial infection. Hence, the patient was treated with
emollient.Abnormal pigmentation was almost resolved, despite of a
persistent high level of total (40 mg/dl) and direct (22 mg/dl)
bilirubin. Patient died after three weeks from severe hepatic
encephalopathy and general state alteration.
Discussion
The spontaneous appearance of green discoloration of the hair, skin, and
nails is unusual (1,2). There are various causes of cutaneous green
discoloration. Differential diagnoses include granulocytic sarcoma,
poisoning (such as by arsenic), acute pancreatitis (Grey Turner and
Cullen signs with the appearance of ecchymotic patches on the abdomen),
eccrine chromhidrosis (which may cause yellow, blue, black, or green
discoloration) and chronic liver disease. Hair and nails can become
green from the deposition of copper or from Pseudomonas infection. Other
causes of green-pigmented lesions, including pseudomonas infection and
exogenous staining that can be excluded by negative Gram stain result
and the absence of greenish substance exposure, respectively (3). Green
pigmentation on the palms and soles in patients with hyperbilirubinemia
is a rare condition, with only 6 reported cases in the literature
(1,3–6). Previous articles have reported that the green pigmentations
are mainly along dermatoglyphic ridges where the eccrine sweat glands
open (4,6,7,9). The etiology of pompholyx is unknown, but associations
with atopy and contact sensitivity have been reported (2,7,8). We
describe an unusual case of pompholyx presenting as green palmar
vesicles in a patient presenting PSC in terminal cirrhosis stage with
severe hyperbilirubinemia. Although pompholyx is spongiotic dermatitis,
the greenish discoloration of the palmoplantar vesicles seen in our
patient cannot be explained by spongiotic changes alone. We hypothesize
that this condition occurs because increased water-soluble bilirubin is
delivered to the intraepidermal sweat glands of patients with
hyperbilirubinemia, where it is deposited into the stratum corneum
(1,2,4). Because of the high density of eccrine sweat glands in the palm
and sole, pompholyx was initially regarded as being associated with
disordered sweat ducts. The vesicular eruptions were thought to arise
primarily in intra-epidermal sweat ducts, accompanied by hyperhidrosis
(8). Pathogenetically, pompholyx was regarded as arising because of
excessive secretion of sweat and dilatation of the intra-epidermal
portion of the eccrine sweat ducts (8).The involvement of sweat units in
the pathogenesis of pompholyx was disputed in reports describing the
development of palmar and plantar vesicles independent of sweat ducts
(8). In addition, considering the role of contact allergens in the
pathogenesis of pompholyx, bile components, such as bilirubin, in sweat,
may have acted as sensitizers, exacerbating the inflammatory spongiosis
(8) . In summary, although sweat units are not involved in the
development of pompholyx, secondary pathological damage to the ducts may
be driven by inflammatory spongiosis. Such involvement of sweat ducts in
the pathogenesis of pompholyx may explain the bile-coloured vesicles of
our patient. In any patient with hyperbilirubinemia and palmoplantar
vesicles, the differential diagnosis should include eccrine
chromhidrosis, a rare condition in which pigment from dyes or
medications are excreted via the eccrine sweat glands (2,3,9). Three
subtypes have been described by Cilliers and de Beer: true eccrine
chromhidrosis, pseudo-eccrine chromhidrosis, and apocrine chromhidrosis
(10,11). Pseudo-eccrine chromhidrosis occurs when the colorless sweat
gets colored on reaching the skin on reaction with exogenous chromogenic
bacterial products such as Corynebacterium , piedraia, bacillus
species, chemicals, paints, and dyes(10,12).True eccrine chromhidrosis
is a less common generalized disorder mostly caused by coloring of the
clear eccrine sweat by dyes, pigments, or metals(10). There is a paucity
of data regarding the eccrine chromhidrosis in medical literature. The
cases of eccrine chromhidrosis to the best of our knowledge reported
till date are summarized
in Table
1.
In addition to these features, intraepidermal spongiosis and
vesiculation can be seen when eccrine chromhidrosis presents as
pompholyx, as seen in our case. Majority of patients had
hyperbilirubinemia secondary to either liver disease, cholelithiasis, or
cancerous processes. It is possible that in our case, because the green
vesicles were located on the palms, where the eccrine sweat gland
density is highest, and along the dermatoglyphic ridges, our patient’s
presentation may actually be a form of eccrine chromhidrosis. This
possibility is supported by proposed pathophysiology that direct
bilirubin is water soluble and may serve as the pigment or stain that is
necessary in the pathologic basis of chromhidrosis (2,10,12). Kanzaki
and Tsuda (4) reported two cases of eccrine chromhidrosis with liver
disease. In hepatocytes associated with liver disease, bile may become
pigmented with brown color. No histological examination had been done
because the patient was seen for a late stage of the eruption. Indeed,
the patient already had desquamative lesions. The bile pigment may be
difficult to highlight because can be washed out during histological
fixation if it is located within the spaces of the eccrine ducts and
vesicles, and not in the cellular spaces (2,10). Possible
pathomechanisms of three essential factors that could contribute towards
the development of pigmentation: (1) increased plasma level of
water-soluble direct bilirubin, (2) high fever with sweating, and (3) a
thick horny layer. The green color is attributable to the switch from
brown-colored bilirubin to green-colored biliverdin by oxidative
processes.
Conclusion:
The case that we reported can be eccrine chromhidrosis resembling the
clinical features of pompholyx with explanation of probable
pathomechanism. To our knowledge, we report the first case of acral
green pigmentation in a patient with PSC.
ACKNOWLEDGMENT: Published with written consent of the patient.
CONFLICTS OF INTEREST : None declared.
AUTHOR CONTRIBUTIONS : BFF and BB: wrote the manuscript. ER and
EA: held the patient in the department. BNH: reviewed the manuscript.