Histological patterns and differential diagnosis of common inflammatory dermatoses : Egyptian Journal of Pathology

Journal Logo


Histological patterns and differential diagnosis of common inflammatory dermatoses

Ramakrishnan, Rathi

Author Information
Egyptian Journal of Pathology: July 2014 - Volume 34 - Issue 1 - p 1-4
doi: 10.1097/01.XEJ.0000446925.85140.b4
  • Free



Cutaneous inflammatory conditions are best diagnosed by a combination approach. The histologic ‘pattern’ approach, direct immunofluorescence (for bullous lesions) and diastase PAS stain together with clinicopathological correlation are adequate for establishing an accurate diagnosis in a vast majority of dermatoses in routine clinical practice (Alsaad and Ghazarian, 2005). The skin shows consistent reaction patterns to various antigenic stimuli, the main categories of which include psoriasiform, lichenoid, spongiotic, granulomatous, vesiculobullous and vasculopathic types. This paper highlights common inflammatory conditions with emphasis on morphological ‘patterns’, differential diagnoses based on these patterns, direct immunofluorescence (where appropriate) and the clinical picture for some of the common lesions that may help clinch the diagnosis.

Pathological considerations

Psoriasiform dermatosis

The classical lesion is psoriasis vulgaris. The epidermis shows a ‘regularly irregular’ pattern of hyperplasia with elongated epidermal ridges, spongiosis, epidermal attenuation overlying the dermal papillae, a thick parakeratotic scale, hypogranulosis (loss of the granular layer), increased basal mitoses and neutrophilic (Munro’s and Kogoj’s) micropustules (Sehgal et al., 2008) in the keratin and the spinous layers (Fig. 1a). A dermal lymphocytic infiltrate is usually present. Clinically, these are keratotic, nonpruritic lesions commonly affecting elbows, knees, trunk, intertriginous areas and genitals (Sehgal et al., 2008).

Fig. 1:
(a) The psoriasiform pattern with intracorneal pustules (H&E ×10). (b) Lichenoid inflammation (H&E ×20). (c) Interface change and cytoid bodies in erythema multiforme (H&E ×20).

The morphological differential diagnosis includes pityriasis rubra pilaris, which shows alternating hyperkeratotic and parakeratotic tiers both in the horizontal and the vertical directions and erythema, but lacks the pustules, suprapapillary thinning and basal mitoses seen in psoriasis. Nail changes may also be present in pityriasis rubra pilaris. Lichen simplex chronicus also shows psoriasiform changes, but scarring of dermal papillae and hypergranulosis are apparent. There is no suprapapillary thinning or neutrophilic pustules as seen in psoriasis. Subcorneal pustular dermatosis, pustular psoriasis and impetigo may also show neutrophils in the keratin layer, but unlike psoriasis, a spongiotic change is prominent. Two other important entities are psoriasiform drug reaction and fungal infections. Both have psoriasiform features and may mimic psoriasis, showing a scaly surface and epidermal pustules. An acute presentation, a history of drug ingestion and the presence of eosinophils usually help distinguish drug rashes from other conditions. Likewise, a simple fungal stain such as d-PAS easily picks up an ‘incognito’ fungal infection that is likely to be missed on H&E.

Lichenoid/interface dermatitis

The prototypic lesion is lichen planus characterized by hyperkeratosis and acanthosis, a prominent granular layer, saw-toothed rete pegs and a prominent interface-obscuring band-like lymphocytic infiltrate (Fig. 1b). Abundant degenerate keratinocytes called ‘colloid’ bodies are seen along the basal layer. Clinically, these lesions present as multiple purple, pruritic or violaceous papules on the trunk or extremities (Sontheimer, 2009). When lichenoid changes affect only the follicular epithelium, lichen plano-pilaris is diagnosed; the latter is a common cause of alopecia. Lichenoid drug reaction(s) may also show similar changes with focal parakeratosis, but vastly increased ‘colloid’ bodies are present along the basal layer, usually with a recognizable number of eosinophils. A history of drug ingestion is often elicited.

Erythema multiforme is a variant of interface dermatitis characterized by the prominence of vacuolar degeneration of the basal layer (Fig. 1c), varying degrees of epidermal necrosis and little lichenoid inflammation. Toxic epidermal necrolysis, lupus erythematosus and graft versus host disease (GvHD) are common lesions in this category. Toxic epidermal necrolysis is an extreme form of erythema multiforme, usually drug-induced, and presents with desquamation and necrosis of the skin. Lupus erythematosus presents either as solitary plaque(s) or as a malar rash, and is histologically characterized by follicular plugging, basal colloid bodies, superficial and deep inflammation, basement membrane thickening and a lack of plasma cells in the infiltrate. GvHD occurs after stem cell (allograft) transplantation and shows ‘satellite cell necrosis’ (single cell death in the epidermis in association with one or more lymphocytes) in the basal layer. The clinical history and the time of allograft are crucial in the distinction of GvHD from lymphocyte recovery (a process of lymphocyte regeneration in the marrow after stem cell transplant, usually within 4 weeks of transplant) and drug reaction (the presence of eosinophils in the latter is helpful but not mandatory).

Other lichenoid conditions that need a mention in this category are lichen nitidus and ‘ashy dermatosis’. The former is seen in children and adolescents, presenting as papular rashes. Histologically, claw-like epidermal extensions limit a localized area of lichenoid inflammation underlying the atrophic epidermis with parakeratosis. Ashy dermatosis also called erythema dyschromicum presents as widespread coalescing papules with epidermal atrophy, basal cell degeneration and pigmentary incontinence.

Spongiotic dermatitis

Acute eczema is the classic example of this entity, developing as a result of severe intraepidermal oedema (spongiosis). Spongiotic vesicles may supervene. There is lymphocytic exocytosis, perivascular dermal inflammation and associated excoriation and lichenification (with chronicity). Eosinophils, occasionally, may be the predominant component in the epidermal vesicles: a condition called eosinophilic spongiosis (Fig. 2a). The main morphological differentials with this picture are prebullous pemphigus/pemphigoid, arthropod bites, atopic eczema, allergic contact dermatitis and drug reactions. Clinical presentation, travel history, food allergies or drug history are usually elicited (McKee et al., 2005).

Fig. 2:
(a) Spongiotic change with eosinophilic spongiosis (H&E ×20). (b) Granuloma annulare showing central necrobiosis (H&E ×20). (c) Necrobiosis lipoidica with panniculitis (H&E ×10).

Granulomatous dermatitis

Besides systemic granulomatous conditions such as mycobacterial and fungal infections, sarcoidosis and Crohn’s disease, there are granulomatous processes that are specific to the skin. These include granuloma annulare (GA), necrobiosis lipoidica, rheumatoid nodule, actinic and elastolytic granulomata. GA present as flesh-coloured, violaceous plaque-like lesions in the proximal acral sites. They are usually superficial, although deep lesions have been described, and typically comprise necrobiotic collagen centrally (Fig. 2b), surrounded by a palisade of histiocytes (complete type) (Heidary et al., 2008). The interstitial (incomplete type) GA shows small spotty foci of necrobiosis rimmed by histiocytes. Necrobiosis lipoidica has strong association with diabetes and shows full-thickness involvement with inflammation of the underlying panniculus (Fig. 1c). Sarcoid-type discrete granulomas may be evident. A rheumatoid nodule usually has a larger zone of central fibrinoid necrosis, commonly found along pressure points. A history of a connective tissue disorder or rhuematoid arthritis antibody-positive arthritis is usually present in the latter. Actinic granulomas develop on sun-exposed sites, mainly on the face, the neck and the trunk. Marked solar elastosis at the periphery with granulomatous inflammation centrally usually clinches the diagnosis. Elastolytic granulomas are seen around degenerate dermal elastic fibres that appear amphophilic and are easily highlighted by routine elastic stains (Miller’s or Elastic Van-Gieson). They may also be associated with perforating collagen/elastic disorders and are often associated with renal impairment.

Vasculopathic dermatitis

Primary vasculitides (polyarteritis nodosa, Wegener’s disease, Henoch–Schönlein purpura and Behcet’s disease) can involve cutaneous vessels (Corwson et al., 2003). They present as leucocytoclastic vasculitis characterized by a fibrinoid change, neutrophilic infiltrate and karyorrhectic debris within the vessel walls (Fig. 3a). Abundant eosinophils may be seen in urticarial, Churg–Strauss syndrome or allergic-type vasculitis. Granuloma faciale and erythema elevatum diutinum are also examples of chronic fibrosing vasculopathy. The former is characterized by tissue eosinophilia, whereas the latter shows a neutrophilic infiltrate. When ‘lymphocytic vasculitis’, basal vacuolation and extravasated red blood cells are seen in the dermis, the vasculitic process is called pityriasis lichenoides chronica (Fig. 3b). These usually present as red-brown scaly plaques, practically anywhere in the body. Differential diagnoses of lymphocytic vasculitis include connective tissue disorders such as lupus, pigmented purpuric dermatosis and annular and gyrate erythemas.

Fig. 3:
(a) Leucocytoclastic vasculitis; Henoch–Schönlein purpura (H&E ×20). (b) Lymphocytic vasculitis with red blood cell extravasation, pityriasis lichenoides chronica (H&E ×20).

Vesiculobullous dermatosis

These lesions are characterized by blister or bullae formation, and are subepidermal or intraepidermal bullae. Common differentials of subepidermal blisters include bullous pemphigoid (eosinophil rich, Fig. 4a), dermatitis herpetiformis (neutrophil rich, Fig. 4b), linear IgA (eosinophils and/or neutrophils), epidermolysis bullous acquisita (neutrophils/eosinophils/cell-poor), erythema multiforme (lymphocytes and histiocytes) and drug-related/toxic epidermal necrolysis (usually cell-poor). Common causes of intraepidermal blisters include pemphigus and variants (eosinophil rich except pemphigus foliaceous where neutrophils are seen), subcorneal pustular dermatosis (neutrophil rich), acantholytic dyskeratosis including Hailey–Hailey, Grover’s and Darier’s disease, the latter characterized by keratohyaline grains and ‘corps ronds’ (solitary cells or groups of acantholytic cells in the malpighian and the corneal layers with pyknotic nuclei, perinuclear halo and eosinophilic cytoplasma; Fig. 4c). These are easily diagnosed by a combination of clinical features: the onset and duration of symptoms, the distribution pattern of the rash, drug history, histological appearances and immunofluorescence features (IgA in dermatitis herpetiformis and linear IgA disease, IgG and C3 in pemphigoid, etc.) (Inchara and Rajalakshmi, 2007).

Fig. 4:
(a) Subepidermal bulla with eosinophils; bullous pemphigoid (H&E ×20). (b) Subepidermal blister with neutrophils, dermatitis herpetiformis (H&E ×20). (c) Corps ronds and grains, Darier’s disease (H&E ×20).


Inflammatory skin diseases may be complex and diagnostically challenging. A knowledge of the histological patterns and interpretation in the light of clinical findings with the help of special stains and immunofluorescence, as appropriate, is usually adequate.


Conflicts of interest

There are no conflicts of interest.


Alsaad KO, Ghazarian D.My approach to superficial inflammatory dermatoses.J Clin Pathology2005;58:1233–1241.
Corwson AN, Mihm MC Jr, Magro CM.Cutaneous vasculitis: a review.J Cutan Pathol2003;30:161–173.
Heidary N, Mengden S, Pomeranz MK.Palisaded neutrophilic and granulomatous dermatosis.Dermatol Online J2008;14:17.
Inchara YK, Rajalakshmi T.Direct immunofluorescence in cutaneous vesiculobullous lesions.Indian J Pathol Microbiol2007;50:730–732.
McKee PH, Calonje E, Granter SR.Pathology of the skin with clinical correlations2005:3rd ed..Philadelphia:Elsevier-Mosby.
Sehgal VN, Dogra S, Srivastava G, Aggarwal AK.Psoriasiform dermatoses.Indian J Dermatol Venereol Leprol2008;74:94–99.
Sontheimer RD.Lichenoid tissue reaction/interface dermatitis: clinical and histological perspectives.J Invest Dermatol2009;129:1088–1099.
©2014Egyptian Journal of Pathology