CED

Clinical dermatology Concise report

Clinical and Experimental Dermatology

Cutaneous annular sarcoidosis developing on a background of

exogenous ochronosis: a report of two cases and review of the
literature
M. J. Moche, S. J. Glassman, D. Modi and W. Grayson*
Division of Dermatology, Department of Medicine and *Division of Anatomical Pathology, School of Pathology, Johannesburg Hospital and the University of
the Witwatersrand, Johannesburg, South Africa
doi:10.1111/j.1365-2230.2009.03485.x

Summary

Exogenous (cosmetic) ochronosis is caused by the long term use of skin-lightening

creams containing hydroquinone. Three cases of systemic sarcoidosis with cutaneous
sarcoidal granulomas, which developed on ochronotic skin were last described by Jacyk
in 1995. Dogliotti and Leibowitz previously reported cases of granulomatous
ochronosis with sarcoid-like histological changes but with no associated systemic
sarcoidosis. We report two additional cases of cutaneous sarcoidal granulomas, which
developed on a background of cosmetic ochronosis in patients recently diagnosed with
systemic sarcoidosis.

Exogenous (cosmetic) ochronosis was first described in

South Africa by Findlay et al.1 in 1975. The first four
cases of granulomatous ochronosis were reported by
Dogliotti and Leibowitz in 1976.2 These cases showed the
characteristic histological changes of sarcoid-like granulomas. Jordaan and Mulligan3 subsequently reported a
case with actinic granuloma-like change in exogenous
ochronosis. There was no evidence of associated systemic
sarcoidosis in either of these cases. In 1995, Jacyk
described six patients who presented with annular
granulomatous lesions, which developed on a background of exogenous ochronosis; three of these cases had
associated systemic sarcoidosis.4 We report two additional cases of cutaneous annular sarcoidal plaques that
developed on a background of cosmetic ochronosis in
patients with newly diagnosed systemic sarcoidosis.

Report
Patient 1 was a 48-year-old black woman, who
presented with a 3-year history of asymptomatic lesions
Correspondence: Dr John Moche, Johannesburg Hospital, Division of Dermatology, Area 553, No 7 York Road, Parktown, South Africa 2193
E-mail: moche@healthbridge.za.net
Conflict of interest: none declared.
Accepted for publication 30 September 2008

on the face and neck. She reported having a dry cough

and fatigue for several weeks. She had been using skinlightening creams with unknown concentrations of
hydroquinone for several years until the mid 1990s. On
physical examination, she was found to have annular
plaques on the right side of the face and neck (Fig. 1a,b).
The preauricular area, helix and inner cavity of the ear
were affected. The lesions on the neck consisted of
scattered comedonal papules, nodules and annular
atrophic plaques. Chest radiography was normal. Full
blood count and chemistry were within normal limits.
She had a raised angiotensin converting-enzyme (ACE)
level (71 U L; normal range 852) and an increased
erythrocyte sedimentation rate (ESR) (30 mm; normal
< 15). Urinary and serum calcium levels were within
normal limits. Serological tests for human immunodeficiency virus (HIV) and syphilis were negative. Histological examination of a biopsy taken from the facial
lesions revealed marked solar elastosis and sarcoidal
granulomas with foreign-body and Langhans giant cells
associated with yellow-brown, banana-shaped ochronotic fibres (Fig. 2a,b). Phagocytosis of fragments of
ochronotic fibres by giant cells (ochrophagocytosis) was
seen, without accompanying elastophagocytosis
(Fig. 2b). Histology of the nodules on the neck also
revealed sarcoidal granulomas associated with localized
foci of dystrophic calcification due to degenerated

 2009 The Author(s)

Journal compilation  2009 British Association of Dermatologists Clinical and Experimental Dermatology, 35, 399402

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Cutaneous annular sarcoidosis developing on a background of exogenous ochronosis M. J. Moche et al.

(a)

(b)

Figure 1 Patient 1. (a) Annular plaques on the face superimposed

on a background of cosmetic ochronosis; (b) brownish papules,

nodules and atrophic plaques on the neck.

ochronotic fibres (Fig. 2c). Calcium deposition was

confirmed with the von Kossa silver stain. Histology of
the comedonal papules on the side of the neck revealed

400

marked swelling and basophilia of the collagen admixed

with ochronotic pigment (Fig. 2d). Colloid milium was
not seen and there was no necrobiosis. Alcian blue
pH 2.5 did not reveal any mucin deposition. Staining
and culture for mycobacteria and fungi gave negative
results. Tuberculin Mantoux test was negative. Chest
radiography showed bilateral hilar and paratracheal
lymphadenopathy with normal lung parenchyma.
These findings were subsequently confirmed by computed tomography (CT). Radiography of the hands
revealed lace-like trabecular pattern of the phalanges
and enlarged nutrient foramina of the metacarpals. The
lung function tests revealed an obstructive pattern.
These features were compatible with sarcoidosis. The
patient was treated with prednisone 30 mg and chloroquine 200 mg daily with clinical improvement of the
systemic symptoms and skin lesions.
Patient 2 was a 58-year-old black woman, who was
admitted to hospital because of dry cough and shortness
of breath. On physical examination, she was found to
have three annular infiltrated plaques on the face
studded with milia-like papules and residual signs of
cosmetic ochronosis (Fig. 3a). Investigations revealed
signs of systemic sarcoidosis: raised ACE level (87 U L),
pulmonary nodules and hilar lymphadenopathy seen on
chest radiography and spiral CT images. Lung function
tests showed an obstructive pattern and the tuberculin
test was negative. An eye examination was normal and
serology tests for HIV and syphilis gave negative results.
Full blood count and chemistry results were within
normal limits, as was serum and urinary calcium. A
dermatology opinion was sought, and records indicated
that the patient had been seen 4 years previously. At
that time she had presented with annular plaques on
the face of about 2 years duration, which were
superimposed on cosmetic ochronosis. Histology of the
lesions had shown sarcoidal granulomas admixed with
cosmetic ochronosis (Fig. 3b). The patient had been lost
to follow-up before systemic investigations were undertaken. A diagnosis of systemic sarcoidosis with cutaneous sarcoidal granulomas which developed on
ochronotic skin was made. The patient was started on
prednisone 30 mg daily and chloroquine 200 mg daily
with marked improvement of the skin lesions. She
continues her regular reviews at both the dermatology
and pulmonology units.
Exogenous ochronosis is caused by the long-term use
of bleaching creams containing hydroquinone in concentrations ranging from 2% to 10%1,9 Some of these
creams also contain phenol and resorcinol. Exposure to
ultraviolet light and concomitant use of potent topical
corticosteroids by African women have been cited as

 2009 The Author(s)

Journal compilation  2009 British Association of Dermatologists Clinical and Experimental Dermatology, 35, 399402

Cutaneous annular sarcoidosis developing on a background of exogenous ochronosis M. J. Moche et al.

(a)

(b)

(c)

(d)

Figure 2 Patient 1. Biopsy from the face showing (a) prominent ochronotic fibres with solar elastosis and (b) multinucleated giant cells
with ochrophagocytosis. Biopsy from the neck showing (c) sarcoidal granulomas associated with calcified and degenerate ochronotic
fibres and (d) basophilia and swelling of collagen admixed with ochronotic fibres. Haematoxylin and eosin, original magnification (a) 20;
(b,c) 40.

(a)

(b)

Figure 3 Patient 2. (a) annular plaque on the face studded with milia-like papules and residualcosmetic ochronosis; (b) sarcoidal
granulomatous infiltrate associated with yellowish-brown ochronotic fibres (haematoxylin and eosin, original magnification 40).

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Journal compilation  2009 British Association of Dermatologists Clinical and Experimental Dermatology, 35, 399402

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Cutaneous annular sarcoidosis developing on a background of exogenous ochronosis M. J. Moche et al.

possible precipitating factors in the development of this

condition. It is classified clinically into three stages:
stage I is characterised by erythema and macular sooty
pigmentation, stage II by intense pigmentation and
caviar-like colloid milia and stage III by papulonodular
lesions. In both our cases, serum ACE levels were raised,
and histology showed sarcoidal granulomas associated
with ochronotic fibres and marked solar elastosis.
Anergy was present and there was evidence of pulmonary involvement.
Findlay and de Beer5 attributed the prominence of
solar elastosis not only to sun damage but also to the
effect of hydroquinone on the fibroblasts, with alteration
of the elastic fibre production and structural make-up.
Swelling of the collagen with increased basophilia is
well described as a precursor stage of colloid milium.1
Sarcoidosis is a multisystemic granulomatous disease of
unknown aetiology. It affects mainly the lungs, lymph
nodes, skin, eyes and musculoskeletal system. In 10
30% of cases, the skin lesions precede systemic disease.
Sarcoidal granulomas may develop in old scars, tattoos,
or areas in which there are foreign bodies such as silica,
talc, beryllium and facial cosmetic fillers.6 Hydroquinone is a foreign material and may also provoke a
sarcoidal reaction. It has been hypothesized that the
foreign material may serve as a nidus for the development of cutaneous sarcoidal granulomas in susceptible
patients.7 The sarcoidal reaction pattern may not
necessarily be reactive or demonstrate a causeeffect
phenomenon, but can be a vital clue to the underlying
subtle systemic disease.8
The present cases emphasize the fact that sarcoidal
granulomas developing on a background of exogenous
ochronosis could be a presentation of sarcoidosis and
that full systemic evaluation should be undertaken.
Legislation was passed in South Africa in 1991 in which

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hydroquinone was banned as a cosmetic product and

declared a scheduled drug.

Acknowledgements
We thank E. Liebenberg, School of Pathology, University
of the Witwatersrand, for the microphotography.

References
1 Findlay GH, Morrison JG, Simson IW. Exogenous
ochronosis and pigmented colloid milium from hydroquinone bleaching creams. Br J Dermatol 1975; 93: 61322.
2 Dogliotti M, Leibowitz M. Granulomatous ochronosis a
cosmetic-induced skin disorder in blacks. S Afr Med J 1979;
56: 75760.
3 Jordaan HF, Mulligan RP. Actinic granuloma-like change in
exogenous ochronosis: case report. J Cutan Pathol 1990; 17:
23640.
4 Jacyk WK. Annular granulomatous lesions in exogenous
ochronosis are a manifestation of sarcoidosis. Am J
Dermatopathol 1995; 17: 1822.
5 Findlay GH, de Beer HA. Chronic hydroquinone poisoning of
the skin from skin-lightening cosmetics. S Afr Med J 1980;
57: 18790.
6 Sidwell RU, Mc Johnson N, Francis N, Bunker CB. Cutaneous sarcoidal granulomas developing after facial cosmetic
filler in a patient with newly diagnosed systemic sarcoidosis.
Clin Exp Dermatol 2005; 31: 20811.
7 Walsh NM, Hanly JG, Tremaine R, Murray S.
Sarcoidosis and foreign bodies. Am J Dermatopathol 1993;
15: 2037.
8 Hanno R, Needelman A, Eiferman RA, Callen JP. Cutaneous
sarcoidal granulomas and development of systemic
sarcoidosis. Arch Dermatol 1981; 117: 2037.
9 Phillips JI, Isaacson C, Carman H. Ochronosis in black South
Africans who used skin lighteners. Am J Dermatopathol
1986; 8: 1421.

 2009 The Author(s)

Journal compilation  2009 British Association of Dermatologists Clinical and Experimental Dermatology, 35, 399402

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