Granulomatous dermatitis

Evert F. Weltevreden MD PhD Tbilisi Georgia 15.11.2013

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Granulomatous dermatitis is a nodular dermatitis that designates infiltrates of inflammatory cells in which histiocytes predominate The name “histiocyte” was proposed by Kiyono (1914) Eli Metchnikoff (1892, 1905) was the first to describe the pahogocytic nature of this type of cell in tissues, after injuring a starfisch larva with a thorn Nowadays these bone marrow derived cells like monocytes and macrophages are taken together under the denomination “mononuclear phagocytes” of the Mononuclear Phagocyte System (MPS, van Furth 1973)

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- Type 1. IgE: specific antibody, direct reaction. acute urticaria / “atopic”

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- Type 2. Ag-Ab complexes: cellular, reaction after 2 – 4 hrs toxicodermia, bullous dermatoses

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- Type 3. Ag-Ab complex deposition in tissue, 4 – 6 hrs urticaria vasculitis

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- Type 4. Cellular > 2 days contact allergy, granulomas, erythema multiforme, GVH

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Sarcoidal

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Tuberculoid

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Palisaded

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Interstitial

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Suppurative

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Sarcoidal - Dermal / subcutaneous, no foreign body, “naked tubercles”

Sarcoidosis Morbus Crohn Melkersson-Rosenthal syndrome Syphilis foreign body, Polarizable;

Silica granuloma

Nonpolarizable;

Tattoo material, e.g. Cobalt

- Perifollicular

Rosacea, miliary lupoid, acne agminata

- Perineural

Leprosy, tuberculoid and dimorphous

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Tuberculoid (caseation necrosis) - Verrucous, hyperkeratotic

Primary cutaneous tuberculosis

- Necrosis slight to moderate

Lupus vulgaris, acne rosacea, acne agminata

- Necrosis severe

Scrofuloderma, miliary tuberculosis

- Plasma cells numerous

Leishmaniasis Syphilis, late secondary Brucellosis

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Palisaded (necrobiotic) - Mucin

Granuloma annulare, deep Granuloma multiforme Borrelia infection

- Degenerated collagen early, thickened bundles late

Necrobiosis lipoidica Meischer’s granuloma

- Fibrin

Rheumatoid nodule

- Urate

Gout

- Vasculitis, fibrin, necrosis

Papulonecrotic tuberculid

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Interstitial - Abudant mucin, degenerated collagen, histiocytes in the upper dermis, PMN’s – eo’s -

Granuloma annulare, superficial

-Degenerated collagen, fibrin, PMN’s ++ and “dust” ++, ghost venules,histiocyts in the reticular (lower) dermis

- Interstitial granulomatous inflammation, PMN’s -, eo’s + lichenoid (vacuolar) epidermal changes

SLE, Rheumatoid disease, drugs (IGD, PN&GD), Allergic granulomatosis; Churg-Strauss syndrome, Rheumatoid vasculitis, M. Wegener, Wells’ syndrome and lymphomatoid granulomatosis Drug eruptions (IGDR)

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Suppurative - Specific infectious agent not identified

- Infectious agent identified

Squames

Follicular cyst rupture Acne inversa

Other foreign bodies

Metals Tattoo materials Splinters Cactus spines

Bacterial Mycobacterial Actinomycotic Fungal Yeast Parasitic

Rhinoscleroma Atypical mycobacterial infl.

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Tuberculosis / atypical mycobacteriosis

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Beryliosis

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Tuberculoid leprosy

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Deep mycosis

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Morbus Crohn (papilary dermis)

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Foreign body reaction

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Miescher-Melkersson-Rosenthal syndrome

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Syphilis, secondary

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Annular elastolytic granuloma

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The diagnosis of sarcoidosis, particular from a skin biopsy, is a diagnosis of exclusion.

Obligate; - polarization for doubly refractile material - look for granulomas following nerves - look for significant necrobiosis / mucinosis - fungal and acid fast stains, PCR Epithelioid cell granulomas, “naked tubercles” Foreigh body and Langhans’ type giant cells Chronology. Lofgren’s syndrome; type A granulomas

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For the diagnosis of granuloma annulare; palisading histiocytes, sometimes (+) interstitial pattern, “busy dermis” Obligate; - polarization for doubly refractile material - look for mucin; colloidal iron stain - look for collagen degeneration - PAS+, Ziehl-Neelsen and GMS stains - Elastica von Giesson (actinic granuloma?)

Ddx; - Syphilis - Tuberculosis - Sarcoidosis - Deep fungal infections - Leishmaniasis - Necrobiosis lipoidica - deep form; rheumatoid nodule

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For the diagnosis of LMDF or acne agminata (unusual form of acne rosacea?)

Obligate; - polarization for doubly refractile material - look for granulomas following nerves - PAS+, Ziehl-Neelsen and GMS stains - PCR /culture Ddx; - Syphilis - Tuberculosis - Sarcoidosis - Deep fungal infections - Leishmaniasis

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Keep always in your mind !

“Busy dermis”, there may be epidermotropism, lichenoid as well as vacuolar, even spongiosis Interstial / granulomatous Obligate; - look for eosinophils - look for mucin and elastolysis - look for granulomas - look for vasculitis - look for atypical lymphocytes Ddx; - Granuloma annulare - Sarcoidosis - Leishmaniasis - Deep fungal infections - Granulomatous MF

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If there is a dermal granulomatous pattern, look to see if it is a sarcoidal, a tuberculoid, a palisading (necrobiotic), an interstitial or a suppurative (infective) one. Is it folliculocentric?

Do polarising microscopy to see is there is any birofrigents indicating foreign bodies.

See if there is any central caseous necrosis, altered collagen or degeneration of elastin.

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See if there are (atypical) lympocytes or plasma cells present.

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Look for vasculitis and presence of PMN’s and eosinophils.

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Ask for special stains for acid and alcohol fast baccillae and do PCR in case of suspected (atypical-) mycobacteriosis. Borrelia antibodies c.q. PCR