JEADV

DOI: 10.1111/jdv.12121

REVIEW ARTICLE

Rosacea under the microscope: characteristic histological
findings
B. Cribier*
Clinique Dermatologique, University Hospital, Strasbourg, France
*Correspondence: B. Cribier. E-mail: Bernard.Cribier@chru-strasbourg.fr

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 specific combinations of
histological features that are highly suggestive of rosacea.
Received: 18 June 2012; Accepted: 28 January 2013

Conflict 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

JEADV 2013, 27, 1336–1343

radicals, also contribute to dermal and blood vessel damage. As
an example, altered innate immune activity can result in overexpression of pro-inflammatory peptides such as cathelicidin. As is
the case in other skin conditions, dermatopathology can provide
valuable information that can help to understand the various
mechanisms of rosacea. Both inflammatory infiltrate and vascular changes can be easily observed, characterized and quantified
under the microscope, using routine staining and immunohistochemistry.
Biopsy is rarely performed for rosacea in routine clinical
practice, as the primary accepted diagnostic features of rosacea are clinical.2,3 Yet biopsy may help where symptoms are
atypical or when the differential diagnosis remains unclear.
Recently, the author performed a large clinicopathologic
study that included collecting biopsies from patients with
dermatologist-diagnosed rosacea (N = 86).4,5 Biopsies were
performed by a dermatologist, who also collected information
about clinical disease presentation. Histological examinations
included haematoxylin and eosin staining and evaluation of
cutaneous changes. Immunohistochemical analyses were performed along with inflammatory infiltrate typing.5 From these
data and other published data, the main histological features
of rosacea were identified (summarized in Table 1). It is
hoped this article will show that histological markers can be
quite useful in diagnosis of rosacea.

© 2013 The Author
Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology

plasma cells) Oedema of superficial dermis ● Visualized as lucent band in superficial papillary and reticular dermis ● Little or no mucin in empty spaces ● Accompanied by inflammatory infiltrate Increased dermal mast cells ● Accompany the enlarged blood vessels ● May play a role in neoangiogenesis Table 2 Histological features of Erythemato-telangiectatic rosacea (ETR) subtype of rosacea ● Enlarged. elastolytic or diffuse ● Demodex mites and sometimes remnants of mites ● No caseation Erythemato-telangiectatic rosacea Erythemato-telangiectatic rosacea (ETR) (Fig 1) is a common rosacea subtype with clinical characteristics that include flushing.4. the number of lymphatic vessels remains relatively normal. D2-40 positive vessels (Fig 5) are. number and size of telangiectatic vessels ● Relatively low number of endothelial cells Perivascular infiltrate ● Surrounds dilated vessels ● Characteristically present at a moderate level ● Composed of mononuclear cells (lymphocytes. intraluminal projections). a marker of lymphatic vessels. angulated telangiectasias and mild lymphocytic infiltrate are the hallmarks of early ETR. exocytosis and acute folliculitis are common ● Solar elastosis ● Absence of retentional elements such as dermal infundibular cysts Table 4 Histological features of granulomatous rosacea Figure 1 Diffuse Erythemato-telangiectatic rosacea (ETR). in the author’s experience.8 Immunohistochemistry demonstrates that such vessels express CD31 but not D2-40. even in the absence of papules or pustules (Fig 3). small and located in the upper and mid dermis. dilated capillaries and venules located in the upper part of the dermis (Fig 2).4 A typical. with few visible endothelial cells. Most cases also exhibit the telltale JEADV 2013. almost always present on histology. is responsible for the clear aspect of the upper dermis and may be due to increased © 2013 The Author Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology . but not specific to rosacea) ● No changes in dermo-epidermal junction Table 3 Histological features of papulo-pustular rosacea (PPR) subtype of rosacea ● Conspicuous superficial and deep inflammation ○ Mixed infiltrate ○ Eosinophils plus plasma cells ● Presence of Demodex mites ● Spongiosis.7 Microscopic examination of ETR biopsies typically shows non-specific features. ● Large granulomas in the superficial and mid dermis ○ Large central empty space ○ Can also be small palisaded. central facial erythema and telangiectasias. dilated capillaries and venules in upper dermis ○ Frequently have bizarre shapes ● Presence of Demodex mites ● Oedema in upper dermis ● Lymphocytic inflammation of varying degrees ● Spongiosis (common. The enlarged vessels. histiocytes. 1336–1343 presence of Demodex within the follicular infundibulum. 27. but one important characteristic change is the presence of enlarged. mostly capillaries.Rosacea under the microscope 1337 Table 1 Histological features of rosacea: summary (2) Abnormality Characteristics in Rosacea Extensive telangiectasias throughout the superficial and middle dermis ● Enlarged lumen ● Unusual shape (tortuous or geometric contours. In rosacea. often exhibit a bizarre shape (Fig 4). Thus. Mild to moderate oedema.6.

with the exception of solid facial oedema. Figure 3 Case of Erythemato-telangiectatic rosacea (ETR) with Demodex present. Also noteworthy are spongiosis and lymphocyte exocytosis within the epidermis. 27. showing dilated superficial vessels with prominent endothelial cells and oedema of the upper dermis.8 Oedema in rosacea is rarely visible to the naked eye. Figure 4 Characteristic bizarre shaped.3.10 The lymphocytic infiltrate is composed of a predominant CD3 + T-cell population JEADV 2013. enlarged venules and capillaries in biopsy of vascular rosacea. Figure 5 Erythemato-telangiectatic rosacea (ETR) stain with D2-40 antibodies on small vessels but not large.9 The inflammatory infiltrate is mainly composed of lymphocytes with a few histiocytes also present.4.Cribier 1338 Figure 2 Biopsy of Erythemato-telangiectatic rosacea (ETR) subtype. number of vessels and defective permeability as well as the discontinuity of endothelial cells. 1336–1343 © 2013 The Author Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology .

Spongiosis and exocytosis are common in the adjacent epidermis. Papulo-pustular rosacea In papulo-pustular rosacea (PPR). neutrophil collections are located around the infundibula. while the infiltrate is generally perifollicular. but in macular lesions is localized in the upper dermis (Table 2). pustules or both.11 small extrafollicular abscesses might aso be observed.13 Specifically. telangiectasias may be present.11 Plasma cells are frequently seen and are an important clue to disease diagnosis. Demodex are almost always present in histological samples from individuals with PPR.10.g. Solar elastosis is also a typical histological finding even if not clinically apparent. The density of the inflammatory infiltrate varies between individuals and can also vary over time. (d) Pustule with collection of neutrophils and Demodex located outside of the follicle. Mast cells are increased in number. unless the patient has concomitant acne vulgaris. Mast cell count is increased in lesional skin. Inflammation typically occurs throughout the upper. and histology shows that while pustules primarily involve the follicle there may also be some involvement outside of the follicle (Table 3). biopsy is indicated to rule out lupus erythematosus (LE). (b) Superficial collection of neutrophils. Ruptured follicles are surrounded by a denser infiltrate and the histological images are similar to those seen in acne. inflammation is much more conspicuous on histology compared with other rosacea subtypes. JEADV 2013. 27. vacuolization of basal keratinocytes and thickening of the basal membrane) which are not observed in rosacea. comedones and dermal infundibular cysts. In the case of LE. the infiltrate is perivascular and perifollicular and there are changes in the dermo-epidermal junction (e. neutrophils and sometimes eosinophils (Fig 6). central facial erythema is characteristic and accompanied by transient papules. eosinophilic debris and ruptured infundibulum in a biopsy of pustular rosacea. and often correlate with the presence of D.12 When papular or pustular lesions are present. 1336–1343 © 2013 The Author Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology . superficial oedema. The prerequisite inflammatory background in ETR subtype is both perivascular and interstitial. Here. When papular lesions are examined histologically.Rosacea under the microscope (at least 70% to 80%) and a minority of CD20 + B cells (10% to 20%). Unlike in folliculitis.7 Comedones are absent. further. the infiltrate density around the capillaries and venules of the upper dermis becomes important. Its presence reflects the probable (b) (d) Figure 6 (a) papulo-pustular rosacea (PPR) biopsy with a large collection of neutrophils beside the follicle on the left. with a minor CD8 + population (<30%) (unpublished personal results). inflammation is typically present in both superficial and deep skin layers. a perifollicular lymphocytic infiltrate is typically present.11 The main diagnostic sign that helps to differentiate rosacea from acne is the absence of retentional elements. mites (Fig 7). T lymphocytes appear mainly as CD4 + .e. When slightly elevated plaques are present. dense lymphocytic inflammation and dilated vessels.10. PPR is characterized by mixed inflammatory infil- (a) (c) 1339 trate.7 Histologically. The follicular or extrafollicular nature of pustules is debated. Spongiotic dermatitis is common but not specific to rosacea. mid and deep dermis. with numerous plasma cells. however. (c) Biopsy with prominent pustule. i. the quantities of mast cells are not well correlated with either severity or duration of the disease.

granulomas might be the sole feature of the disease. Granulomas are commonly observed in rosacea. The infiltrate is mainly lymphocytes and neutrophils around the enlarged infundibula. both findings strengthen theories of Demodex involvement in this subtype.17 Other types of granulomas can be observed. 27. expressive follicles in the area of the phyma are sometimes visible. but is generally less conspicuous than in PPR. mites or eosinophilic remnants of Demodex in the centre of histiocyte collections (Fig 8). central empty space surrounded by a layer of neutrophils and numerous periph- (a) Demodicosis Demodicosis is a broad term applied to skin conditions due to D. elastolytic or more diffuse granulomas. JEADV 2013. but the structure of the gland is normal. as in senile sebaceous hyperplasia. In certain cases.15 Histologically. Enlargement of infundibula is associated with the formation of epidermal cysts that can rupture and induce inflammation.19 Demodex mites are common. irregular surface nodularities and hypertrophy (Fig 9). i.18 The sebaceous lobules are extremely large.7 Telangiectasias and patulous. rhinophyma is characterized by increased volume of sebaceous glands and fibrosis (Fig 10). small palisaded. (b) Figure 8 (a) Clinical presentations of granulomatous rosacea. Inflammation is always present. it is not possible to differentiate rosacea from demodicosis based on histopathological analysis.g. granulomatous rosacea is characterized by large granulomas of the superficial and mid dermis that can include a large. Granulomatous rosacea Variants in clinical practice Figure 7 Pustular rosacea with remnants of Demodex within the neutrophil infiltrate.16 Serial sections often show D. mites.e. 1336–1343 © 2013 The Author Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology .15. without prominent dilated vessels (e. The infundibula are enlarged and filled with lamellar keratin. (b) Histology of granulomatous rosacea. In severe cases with scaling.7 Histologically. the signs and symptoms of ETR and PPR may also be present (Table 4). eosinophilic debris and microorganisms. Phymatous rosacea pathophysiological role of ultraviolet (UV) exposure and associated free radical damage in rosacea.14 and are not restricted to the centrofacial area.15 The lesions are typically hard. lupoid rosacea or granulomatous perioral dermatitis).4 Phymatous rosacea often involves the nose and includes thickened skin.Cribier 1340 eral histiocytes admixed with lymphocytes. Small granulomas might also be present. including several variants that are clinically similar to rosacea.20 In the author’s experience. red–brown to yellow papules that are found in a symmetrical distribution.

PAS staining can show Malassezia yeasts. 27. 1336–1343 © 2013 The Author Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology . JEADV 2013. Seborrhoeic dermatitis/rosacea Certain cases of rosacea exhibit distinct signs of seborrhoeic dermatitis (Fig 11.21 In these cases.21 (a) Summary Rosacea has a multifactorial pathology that includes both inflammatory processes and a prominent vascular component. (c) rhinophyma with fibrosis and dilated vessels at top. histopathology shows mixed features. (b) rhinophyma biopsy with large cystic space. i. dilated superficial vessels (a feature not present in classic seborrhoeic dermatitis). On histology. characteristic components include enlarged and strangely shaped small blood vessels.e.Rosacea under the microscope 1341 Figure 9 Rhinophyma. and perivascular and interstitial inflammation.12). Oedema is often present and visible. oedema and perivascular/ perifollicular infiltrate associated with foci of parakeratosis. Figure 11 Rosacea with seborrhoeic dermatitis. (b) (c) Figure 10 (a) Enlarged sebaceous glands and peripheral fibrosis in biopsy of rhinophyma (hypertrophic rosacea). parakeratosis with numerous neutrophils can be seen at the surface of pustular lesions.

which is usually visible on histology and often associated with spongiotic skin alterations.23 The changes in size and shape of small blood vessels in rosacea may explain a lack of permeability that leads to oedema. the confluence of vasodilation plus increased blood flow and higher local temperature may encourage colonization and proliferation of Demodex. Agapitos E. telangiectasia. Epub 2004/10/02. J Am Acad Dermatol 2002. 27. Mazzatenta C.5 Lymphocytic infiltrates can be seen. successfully treated with isotretinoin and ketotifen. 3): S184–S191. suggesting an infectious reaction. Cribier B. Layton A. Arch Dermatol Res 2008. Kennedy Carney C. Cantrell W. it seems likely that the subjective signs and symptoms of rosacea may be related to the proximity of the superficial dermal vessels and nerve fibres. Aubert J et al. PubMed PMID: 2974268. Rubegni P. 209: 177–182.22 There is a high rate of Demodex carriage in all clinical subtypes of rosacea. (b) parakeratosis containing neutrophils and dense lymphocytic infiltrate. Ioannidis E.5 It is possible that the vascular abnormalities of rosacea. PubMed PMID: 9585896. Wilkin J. Epub 2012/01/04. Giorgino G. Epub 2007/12/12. 3 4 5 6 7 8 9 10 11 12 References 1 Steinhoff M. eng.5 The association between vascular changes and inflammation remains unclear. Patsouris E. J Eur Acad Dermatol Venereol 2011. Tsagroni E. it may have a role in stimulating inflammation via its resident bacteria or proteins from bacterial degradation. Aroni K. eng. cellular. systemic and light-based therapies. PubMed PMID: 19907406. Clinical. G Ital Dermatol Venereol 2009. primarily in capillaries. Aroni K. eng. Picardo M. Granulomas are also common and may be associated with elastosis. PubMed PMID: 18071725. Lazaris AC. Epidemiology of rosacea: updated data. eng. Cribier B. Epub 1998/05/20. PubMed PMID: 22183097. Epub 1988/01/01. and while similar in cellular makeup with other conditions such as LE. Peltre B. 138(Suppl. 46: 584–587. PubMed PMID: 22183096. fre. eng. Neumann E. Jansen T. but identification of pro-inflammatory mechanisms of innate immunity in rosacea may help explain formation of telangiectasia in the papulo-pustular form of the disease. Dreno B. Dahl M. Histological and immunohistological study of vascular and inflammatory rosacea. eng. Epub 2009/ 11/13. Chosidow O. Epub 2011/11/15.global diversity and optimized outcome: proposed international consensus from the Rosacea International Expert Group. Pathophysiology of rosacea: redness. Br J Dermatol 1997. Cribier B. Capillaropathy and capillaroneogenesis in the pathogenesis of rosacea. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea.5 Because the mite is present in >60% of ETR. Frithz A. Rosacea . Perrigouard C. Epub 2002/03/22. Elewski BE.5 Finally. De Aloe G. 138(Suppl. Dermatology 2004. PubMed PMID: 20586834. 25: 188–200.5 These histological markers of rosacea can be quite useful in making and excluding a diagnosis. Solid persistent facial oedema (Morbihan’s disease) following rosacea. Plasma cells and eosinophils are not uncommon. Ann Dermatol Venereol 2011. the infiltrate is typically less pronounced in rosacea.Cribier 1342 (a) (b) Figure 12 (a) Biopsy showing Demodex mite. 115: 801–806. Epub 2010/07/01. Patsouris E.5 The infiltrate contains mainly T cells.5 In addition. Buddenkotte J. eng. 3): S179–S183. thick parakeratosis and inflammation. 137: 1020–1021. 37: 263–266. 15: 2–11. © 2013 The Author Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology . Epub 1998/02/21. Ramelet AA. eng. PubMed PMID: 9470933. Elewski BE. 144: 673–688. and rosacea. Detmar M et al. Ann Dermatol Venereol 2011. eng. Int J Dermatol 1998. Kavantzas N. Rosacea: a review of current topical. and molecular aspects in the Pathophysiology of Rosacea. 2013. Rosacea: a clinicopathological approach. primarily CD4 + lymphocytes. Draelos Z. Tsagroni E. A study of the pathogenesis of rosacea: how angiogenesis and mast cells may participate in a complex multifactorial process. J Investig JEADV 2013. are a form of photodamage. PubMed PMID: 22076321.14. PubMed PMID: 15459529. 1336–1343 2 Dermatol Symp Proc 2011. Fimiani M. Ann Dermatol Venereol 1988. Rosacee: etude histopathologique de 75 cas. 300: 125–131. 140: 21–29. Perroulaz G. [Rosacea: histopathologic study of 75 cases]. PubMed PMID: 11907512.

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