Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
DOI: 10.1111/jdv.12121
REVIEW ARTICLE
Abstract
Rosacea is a common facial dermatosis that is seldom biopsied; thus, histological aspects have not been well described.
Biopsies are generally performed in the presence of atypical symptoms (e.g. granulomas). Differential diagnosis with sarcoidosis, lupus miliaris or lupus erythematosus is another indication for biopsy. There are few published studies addressing the microscopic aspects of rosacea and describing the histological and immunohistochemical features of this
disease. While some textbooks consider the microscopic signs of rosacea to be non-diagnostic, experienced dermatopathologists are generally able to make the diagnosis via histology. This article discusses the specic combinations of
histological features that are highly suggestive of rosacea.
Received: 18 June 2012; Accepted: 28 January 2013
Conict of interest
ne, Intendis); clinical trial (BiorgaConsultant (Galderma International); invited speaker (Galderma, Pierre Fabre, Ave
Bailleul)
Introduction
Rosacea manifests in a variety of clinical presentations. Facial
redness may be accompanied by papules and/or pustules, and
in some cases, ocular involvement or phymatous changes.
The condition encompasses a range of pathologic mechanisms
that are relatively poorly understood, although most researchers now agree that the pathophysiology involves two primary
factors: vascular abnormalities and inflammation. It has
recently been proposed that innate immune mechanisms and
changes in regulation of the neurovascular system come
together to initiate and perpetuate rosacea, although the exact
mechanisms and corresponding reactions have yet to be
elucidated.1
A full discussion of rosacea pathophysiology is beyond the
scope of this article, but mention of several factors may be helpful when considering the histological manifestations of the disease. Environmental triggers such as sunlight exposure and
temperature change are thought to play a part in disease pathophysiology by contributing to vascular changes in susceptible
individuals. Vascular abnormalities result in blood vessel dilation with increased capillary permeability and oedema, which in
turn provide a favourable setting for Demodex colonization and
proliferation. Demodex stimulates inflammation, increasing the
likelihood of papulo-pustular or granulomatous lesions. Additional inflammatory actions, including the release of oxygen free
1337
Characteristics in Rosacea
Enlarged lumen
Unusual shape (tortuous or geometric contours, intraluminal projections), number and size of
telangiectatic vessels
Relatively low number of endothelial cells
Perivascular inltrate
Erythemato-telangiectatic rosacea
Erythemato-telangiectatic rosacea (ETR) (Fig 1) is a common
rosacea subtype with clinical characteristics that include flushing, central facial erythema and telangiectasias.6,7 Microscopic
examination of ETR biopsies typically shows non-specific
features, but one important characteristic change is the presence
of enlarged, dilated capillaries and venules located in the upper
part of the dermis (Fig 2). Most cases also exhibit the telltale
Cribier
1338
Figure 2 Biopsy of Erythemato-telangiectatic rosacea (ETR) subtype, showing dilated supercial vessels with prominent endothelial cells and oedema of the upper dermis. Also noteworthy are
spongiosis and lymphocyte exocytosis within the epidermis.
The inflammatory infiltrate is mainly composed of lymphocytes with a few histiocytes also present.10 The lymphocytic infiltrate is composed of a predominant CD3 + T-cell population
Papulo-pustular rosacea
In papulo-pustular rosacea (PPR), central facial erythema is
characteristic and accompanied by transient papules, pustules or
both.7 Comedones are absent, unless the patient has
concomitant acne vulgaris; telangiectasias may be present.7 Histologically, PPR is characterized by mixed inflammatory infil-
(a)
(c)
1339
(b)
(d)
Figure 6 (a) papulo-pustular rosacea (PPR) biopsy with a large collection of neutrophils beside the follicle on the left, supercial oedema,
dense lymphocytic inammation and dilated vessels. (b) Supercial collection of neutrophils, eosinophilic debris and ruptured infundibulum in a biopsy of pustular rosacea. (c) Biopsy with prominent pustule. (d) Pustule with collection of neutrophils and Demodex located
outside of the follicle.
Cribier
1340
Phymatous rosacea
pathophysiological role of ultraviolet (UV) exposure and associated free radical damage in rosacea.4
Phymatous rosacea often involves the nose and includes thickened skin, irregular surface nodularities and hypertrophy
(Fig 9).7 Telangiectasias and patulous, expressive follicles in the
area of the phyma are sometimes visible; the signs and symptoms of ETR and PPR may also be present (Table 4).7 Histologically, rhinophyma is characterized by increased volume of
sebaceous glands and fibrosis (Fig 10).18 The sebaceous lobules
are extremely large, as in senile sebaceous hyperplasia, but the
structure of the gland is normal. The infundibula are enlarged
and filled with lamellar keratin, eosinophilic debris and microorganisms.19 Demodex mites are common.
Enlargement of infundibula is associated with the formation
of epidermal cysts that can rupture and induce inflammation.
Inflammation is always present, but is generally less conspicuous
than in PPR. The infiltrate is mainly lymphocytes and neutrophils around the enlarged infundibula. Small granulomas might
also be present.
Granulomatous rosacea
(a)
Demodicosis
(b)
Figure 8 (a) Clinical presentations of granulomatous rosacea. (b) Histology of granulomatous rosacea.
1341
Figure 9 Rhinophyma.
Seborrhoeic dermatitis/rosacea
(a)
Summary
Rosacea has a multifactorial pathology that includes both
inflammatory processes and a prominent vascular component.
On histology, characteristic components include enlarged and
strangely shaped small blood vessels, and perivascular and interstitial inflammation. Oedema is often present and visible.
(b)
(c)
Figure 10 (a) Enlarged sebaceous glands and peripheral brosis in biopsy of rhinophyma (hypertrophic rosacea), (b) rhinophyma biopsy
with large cystic space, (c) rhinophyma with brosis and dilated vessels at top.
Cribier
1342
(a)
(b)
Figure 12 (a) Biopsy showing Demodex mite, thick parakeratosis and inammation, (b) parakeratosis containing neutrophils and dense
lymphocytic inltrate.
5
6
10
11
12
References
1 Steinhoff M, Buddenkotte J, Aubert J et al. Clinical, cellular, and
molecular aspects in the Pathophysiology of Rosacea. J Investig
Dermatol Symp Proc 2011; 15: 211. PubMed PMID: 22076321. Epub
2011/11/15. eng.
Kennedy Carney C, Cantrell W, Elewski BE. Rosacea: a review of
current topical, systemic and light-based therapies. G Ital Dermatol
Venereol 2009; 144: 673688. PubMed PMID: 19907406. Epub 2009/
11/13. eng.
Elewski BE, Draelos Z, Dreno B, Jansen T, Layton A, Picardo M. Rosacea
- global diversity and optimized outcome: proposed international
consensus from the Rosacea International Expert Group. J Eur Acad
Dermatol Venereol 2011; 25: 188200. PubMed PMID: 20586834. Epub
2010/07/01. eng.
Cribier B. Pathophysiology of rosacea: redness, telangiectasia, and rosacea. Ann Dermatol Venereol 2011; 138(Suppl. 3): S184S191. PubMed
PMID: 22183097. Epub 2012/01/04. eng.
Perrigouard C, Peltre B, Cribier B. Histological and immunohistological
study of vascular and inflammatory rosacea. 2013; 140: 2129.
Chosidow O, Cribier B. Epidemiology of rosacea: updated data. Ann
Dermatol Venereol 2011; 138(Suppl. 3): S179S183. PubMed PMID:
22183096.
Wilkin J, Dahl M, Detmar M et al. Standard classification of rosacea:
report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol 2002; 46: 584587.
PubMed PMID: 11907512. Epub 2002/03/22. eng.
Neumann E, Frithz A. Capillaropathy and capillaroneogenesis in the
pathogenesis of rosacea. Int J Dermatol 1998; 37: 263266. PubMed
PMID: 9585896. Epub 1998/05/20. eng.
Mazzatenta C, Giorgino G, Rubegni P, De Aloe G, Fimiani M. Solid persistent facial oedema (Morbihans disease) following rosacea, successfully
treated with isotretinoin and ketotifen. Br J Dermatol 1997; 137:
10201021. PubMed PMID: 9470933. Epub 1998/02/21. eng.
Ramelet AA, Perroulaz G. [Rosacea: histopathologic study of 75 cases].
Ann Dermatol Venereol 1988; 115: 801806. PubMed PMID: 2974268.
Epub 1988/01/01. Rosacee: etude histopathologique de 75 cas. fre.
Aroni K, Tsagroni E, Kavantzas N, Patsouris E, Ioannidis E. A study of
the pathogenesis of rosacea: how angiogenesis and mast cells may participate in a complex multifactorial process. Arch Dermatol Res 2008; 300:
125131. PubMed PMID: 18071725. Epub 2007/12/12. eng.
Aroni K, Tsagroni E, Lazaris AC, Patsouris E, Agapitos E. Rosacea: a clinicopathological approach. Dermatology 2004; 209: 177182. PubMed
PMID: 15459529. Epub 2004/10/02. eng.
1343