1233 J Clin Pathol: first published as 10.1136/jcp.2005.027151 on 25 November 2005. Downloaded from REVIEW My approach to superficial inflammatory dermatoses K O Alsaad, D Ghazarian ............................................................................................................................... J Clin Pathol 2005;58:1233–1241. doi: 10.1136/jcp.2005.027151 Superficial inflammatory dermatoses are very common and diagnosis of inflammatory skin diseases, there are limitations to this approach. The size of the comprise a wide, complex variety of clinical conditions. skin biopsy should be adequate and representa- Accurate histological diagnosis, although it can sometimes tive of all four compartments and should also be difficult to establish, is essential for clinical include hair follicles. A 2 mm punch biopsy is too small to represent all compartments, and often management. Knowledge of the microanatomy of the skin insufficient to demonstrate a recognisable pat- is important to recognise the variable histological patterns tern. A 4 mm punch biopsy is preferred, and of inflammatory skin diseases. This article reviews the non- usually adequate for the histological evaluation of most inflammatory dermatoses. However, a vesiculobullous/pustular inflammatory superficial larger biopsy (6 mm punch biopsy), or even an dermatoses based on the compartmental microanatomy of incisional biopsy, might be necessary in panni- the skin. culitis or cutaneous lymphoproliferative disor- ders. A superficial or shave biopsy should be ........................................................................... avoided, because it might be misleading, produ- cing an erroneous pattern and diagnosis. he histological diagnosis of cutaneous inflammatory diseases can be confusing, PRACTICAL POINTS even for the most experienced pathologist. T In the histological evaluation of skin for inflam- This is because the immune system within the matory dermatoses, a clinicopathological correla- skin has limited ways in which it reacts and tion is essential, and plays an important role in responds to an antigenic stimulus, and many achieving the diagnosis. The patient’s age and inflammatory diseases do not show specific relevant clinical history, in addition to the site histological features. In view of this complexity and commonality, histological patterns of recog- from which the skin biopsy was obtained, should nition are beneficial for the rapid development of be provided to the pathologist. After proper a differential diagnosis. This can be achievable by fixation and processing, three deeper haematox- being familiar with the microanatomy of the skin ylin and eosin stained sections and one section and its regional variations, in addition to the stained with periodic acid Schiff (PAS) for basic structural alterations that can occur in evaluation of the epidermal basement mem- http://jcp.bmj.com/ different pathological conditions. This review is brane, blood vessels, and the presence of fungal oriented towards the recognition of the histolo- organisms are considered sufficient for micro- gical patterns seen in non-vesiculobullous/pust- scopic evaluation. The need for deeper sections ular inflammatory superficial dermatoses that and special stains varies from one case to involve the epidermis and papillary dermis, using another, and additional tasks can be ordered a schematic approach. when necessary. Special stains that might be beneficial in establishing a diagnosis of inflam- matory dermatoses include Martius-Scarlet blue on September 26, 2021 by guest. Protected copyright. THE ANATOMICAL COMPARTMENTS/ stain for fibrin, colloidal iron Hale’s for acid UNITS OF THE SKIN mucin, Prussian blue for iron, toluidine blue for From the practical point of view, the skin is mast cells, Fontana Masson for melanin pig- divided into four anatomical compartments or ment, elastic stain for perforating disorders and units: demonstration of elastic tissue, Von Kossa for (1) The first compartment/unit includes the calcium deposits, and Congo red for amyloid. epidermis, papillary dermis, and superficial Gram stain and Gomori methenamine silver vascular plexus. These structures are inter- stain can be helpful in demonstrating bacterial See end of article for and fungal microorganisms, respectively. authors’ affiliations related and mutual. ....................... (2) The second compartment/unit consists of the Correspondence to: reticular dermis and the deep vascular ‘‘Immunofluorescence studies have an essen- Dr K O Alsaad, plexus. tial role in diagnosing immunologically Department of Laboratory (3) The third compartment/unit consists of the related inflammatory skin diseases, specifi- Medicine and cally vesiculo-bullous diseases and vasculitis’’ Pathobiology, University of pilosebaceous units, the eccrine glands, and Toronto, University Health in certain anatomical locations, the apocrine Network, Toronto, glands. Immunohistochemistry has a limited role, Ontario, Canada; (4) The fourth compartment/unit is the subcu- although it can be useful in certain clinical [email protected] taneous tissue (panniculum). Accepted for publication Abbreviations: GVHD, graft versus host disease; HIV, 26 April 2005 Although using a compartmental approach to human immunodeficiency virus; PAS, periodic acid Schiff; ....................... establish the reaction pattern facilitates the PVI, perivascular inflammatory infiltrate www.jclinpath.com 1234 Alsaad, Ghazarian J Clin Pathol: first published as 10.1136/jcp.2005.027151 on 25 November 2005. Downloaded from Table 1 Subclassification of inflammatory dermatoses Compartment one without epidermal changes (superficial perivascular (epidermis and superficial dermis) inflammation) Type of inflammatory cell infiltrate Lymphocytic (most common) Non vesiculobullous/ Pustular Vesiculobullous Lymphoeosinophilic pustular lesions dermatosis lesions Lymphoplasmacytic Mast cell infiltrate Lymphohistiocytic Neutrophilic Without epidermal changes With epidermal changes Figure 1 Classification of the inflammatory dermatoses involving the Inflammatory dermatoses without epidermal changes first compartment. The inflammatory skin dermatoses without epidermal changes are manifested histologically by a superficial conditions, such as characterising the neoplastic CD4+ T cell perivascular inflammatory infiltrate (PVI). This reactive population in mycosis fungoides and the CD4+ and CD8+ T pattern is induced by many conditions. The type of cell populations in patients with human immunodeficiency inflammatory cell infiltrate is different from one condition disorder (HIV). It is worthwhile mentioning that the CD8+ T to another, allowing further subclassification of the PVI into cell population is the predominant subtype in HIV derma- six groups (table 1). toses. Immunofluorescence studies have an essential role in diagnosing immunologically related inflammatory skin dis- PVI with a predominant lymphocytic infiltrate eases, specifically vesiculo-bullous diseases and vasculitis. This is the most common type of PVI. Many conditions can Electron microscopy is of limited value, but may be helpful in result in a lymphocytic PVI. Common causes are immuno- certain vesiculo-bullous diseases, mycosis fungoides, and logical and non-immunological cutaneous drug eruption1–4— Langerhans cell histiocytosis. particularly secondary to antibacterials5–7 (fig 3), urticarial reactions,89 viral exanthema, infestation, and insect bites. Other less common conditions are fungal infections, pig- A PRAGMATIC APPROACH mented purpuric dermatoses,10–12 erythema annulare centri- Most common superficial inflammatory dermatoses involve fugum,13 14 and other gyrate erythemas. the first compartment/unit of the skin. The most common pattern of reaction encountered is the superficial perivascular PVI with lymphoeosinophilic infiltrate inflammatory infiltrate. A transient inflammatory stimulus Many conditions that cause PVI with a predominant results in slight hyperaemia and a mild perivascular lymphocytic infiltrate can present with a lymphoeosinophilic lymphocytic infiltrate. If the stimulus persists, interstitial infiltrate. These conditions include drug reactions (fig 4), oedema and endothelial swelling develop. With further urticarial reactions, a prevesicular early stage of bullous stimulation, involvement of the overlying epidermis occurs. pemphigoid, insect bites (fig 5), infestations, and HIV related Inflammatory dermatoses involving the first compartment of dermatoses.15 16 In pregnant women, pruritic urticarial http://jcp.bmj.com/ the skin are divided into three main categories (fig 1): (1) papules and plaques of pregnancy are characterised by a non-vesiculobullous/pustular lesions, (2) pustular derma- perivascular lymphoeosinophilic inflammatory infiltrate in toses, and (3) vesiculo-bullous lesions. The non-vesiculobul- skin biopsies.17 18 lous/pustular lesions, the focus of this review, are divided into two categories based on the presence or absence of PVI with lymphoplasmacytic infiltrate epidermal changes. When epidermal changes are present, A prominent plasma cell component of the inflammatory they are further subdivided into spongiotic dermatitis, infiltrate may be seen adjacent to an area of trauma, on September 26, 2021 by guest. Protected copyright. interface dermatitis, and psoriasiform dermatitis (fig 2). ulceration, or scar. It is also seen in cases of rosacea, secondary syphilis, and erythema chronicum migrans, which is pathognomonic of Lyme’s disease.19 The patch stage