Clinics in Dermatology (2014) 32,47–65 Granulomatous disorders Suhan Günaştı,MD⁎, Varol L. Aksungur, MD Department of Dermatology, School of Medicine, Cukurova University, Adana, Turkey Abstract Almost all granulomatous skin disorders can cause red lesions on the face. Such disorders may include many bacterial, fungal, or parasitic infections, noninfectious inflammatory disorders, foreign body reactions, and even neoplasms. Clinically, they usually present with papules, plaques, nodules, and/or abscesses, which may ulcerate. It may be helpful in their differential diagnosis to define certain clinical patterns, such as multiple and discrete papules, necrotic or umbilicated papules or nodules, annular plaques, vegetative plaques or tumors, verrucous plaques or tumors, abscesses and/or sinuses, and lymphocutaneous pattern. Some disorders, such as sarcoidosis, can cause a wide variety of lesions. We accept that cutaneous leishmaniasis is also among such great imitators. © 2014 Elsevier Inc. All rights reserved. Introduction histoplasmosis, and amebiasis) is an neutrophilic abscess surrounded by histiocytes and lymphocytes. Foreign body Granulomatous disorders are a large group of conditions granuloma is an accumulation of histiocytes, giant cells, that share the common denominator, namely, histologic neutrophils, and lymphocytes around an extrinsic or intrinsic “ evidence of granuloma formation. A granuloma is an body. Two more categories are lichenoid and granuloma- ” “ ” organized collection of epithelioid histiocytes. Various tous dermatitis and granulomatous vasculitis. The former adjectives have been used to categorize granulomas, (seen in lichen nitidus and lichen striatus) is characterized by including sarcoidal, tuberculoid, palisaded, suppurative, a bandlike lymphocytic infiltrate with a concomitant 3 and foreign body.1,2 Sarcoidal granuloma (seen in sarcoid- granulomatous inflammation. The latter (seen in Wegener osis, orofacial granulomatosis, and tattoo granuloma) is a granulomatosis and Churg-Strauss syndrome) is character- well-circumscribed collection of epithelioid histiocytes with ized by an angiocentric granulomatous inflammation or by a relatively few or no lymphocytes. Tuberculoid granuloma granulomatous inflammation unrelated to vessels accompa- 4 (seen in lupus vulgaris, syphilis, and leishmaniasis) is a well- nied by necrotizing vasculitis. These categories are not circumscribed collection of epithelioid histiocytes in associ- absolute; for example, sarcoidosis may also demonstrate 2 ation with a surrounding relatively dense infiltrate of tuberculoid or foreign body granulomas. lymphocytes. Langhans giant cells and central necrosis Almost all granulomatous skin disorders can cause red may also present. Palisaded granuloma (seen in granuloma lesions on the face. Table 1 gives a comprehensive, but not annulare [GA], necrobiosis lipoidica, and necrobiotic complete, list of such disorders. Facial red lesions caused by xanthogranuloma) consists of histiocytes arranged in a a granulomatous inflammation demonstrate a wide variety of palisade fashion at the periphery of a necrobiotic area of clinical morphologies. Some disorders have many clinical collagen. Suppurative granuloma (seen in rhinoscleroma, presentations; some disorders have no distinctive clinical presentation. It is almost impossible to categorize these ⁎ Corresponding author. Tel.: +903223386060 (3150-52). disorders according to their clinical presentations; however, E-mail address: [email protected] (S. Günaştı). it will be helpful to list the disorders capable of causing a 0738-081X/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clindermatol.2013.05.025 48 S. Günaştı and V.L. Aksungur Table 1 Granulomatous disorders capable of causing facial certain clinical pattern, as in Table 2. In this contribution, red lesions granulomatous disorders, which can cause facial red lesions, Bacterial infections Noninfectious inflammatory will be briefly discussed in the context of clinical disorders morphology with a special emphasis on the face. Tuberculosis Lichen nitidus Tuberculous chancre Lichen striatus Scrofuloderma Granulomatous rosacea Bacterial infections Miliary tuberculosis Lupus miliaris disseminatus faciei Tuberculous gumma Granulomatous periorificial Tuberculosis dermatitis Tuberculosis Idiopathic facial aseptic granuloma verrucosa cutis Tuberculous chancre is primary inoculation tuberculosis Lupus vulgaris Sarcoidosis of the skin.5 Several weeks after the inoculation, an Papulonecrotic Blau syndrome erythematous papule or nodule appears, which eventually tuberculid ulcerates. Regional lymphadenopathy may follow the skin Erythema induratum Interstitial granulomatous of Bazin dermatitis and palisaded neutrophilic and granulomatous dermatitis Table 2 Certain clinical patterns of granulomatous skin Lichen scrofulosorum Orofacial granulomatosis lesions on the face and their causes Atypical mycobacterial Crohn disease infections Multiple and discrete Leishmaniasis, demodicidosis, Leprosy (tuberculoid Granuloma annulare papules granulomatous rosacea, lupus miliaris and dimorphous) disseminatus faciei, granulomatous Syphilis (secondary and Actinic granuloma periorificial dermatitis, sarcoidosis, tertiary) Wegener granulomatosis Rhinoscleroma Necrobiosis lipoidica Grouped or confluent Syphilis, lichen scrofulosorum, Blau Cat-scratch disease Necrobiotic xanthogranuloma papules syndrome, cactus spine granuloma Actinomycosis Wegener granulomatosis Necrotic or umbilicated Miliary tuberculosis, papulonecrotic Nocardiosis Churg-Strauss syndrome papules or nodules tuberculid, histoplasmosis, Botryomycosis cryptococcosis, alternariosis, Pyoderma vegetans penicilliosis marneffei, granuloma Fungal infections Foreign body reactions annulare, Wegener granulomatosis, Kerion Gout Churg-Strauss syndrome Majocchi granuloma Ruptured cysts Urticarial plaques Churg-Strauss syndrome Candida granuloma Tattoo Yellowish brown Necrobiotic xanthogranuloma Coccidioidomycosis Hyaluronic acids plaques or tumors Histoplasmosis Silicone Annular plaques Leprosy, syphilis, leishmaniasis, Cryptococcosis Silica sarcoidosis, actinic granuloma Blastomycosis Metals Centrally atrophic Lupus vulgaris, syphilis, Paracoccidioidomycosis Cactus spines plaques blastomycosis, chromoblastomycosis Sporotrichosis Neoplasms Vegetative plaques or Pyoderma vegetans, blastomycosis, Chromoblastomycosis Granulomatous mycosis fungoides tumors paracoccidioidomycosis, Phaeohyphomycosis rhinosporidiosis, leishmaniasis Alternariosis Verrucous plaques or Tuberculosis verrucosa cutis, Eumycetoma tumors coccidioidomycosis, blastomycosis, Lobomycosis paracoccidioidomycosis, Rhinosporidiosis chromoblastomycosis, Entomophthoromycosis rhinosporidiosis, leishmaniasis Zygomycosis Cutaneous horns Candida granuloma, rhinosporidiosis Penicilliosis marneffei Keloidlike lesions Lobomycosis Algal infections Abscesses and/or Scrofuloderma, tuberculous gumma, Protothecosis sinuses cat-scratch disease, actinomycosis, Protozoal infections nocardiosis, botryomycosis, Leishmaniasis phaeohyphomycosis, eumycetoma, Amebiasis metal granuloma Parasitic infections Boggy plaques Kerion Demodicidosis Lymphocutaneous Nocardiosis, coccidioidomycosis, pattern sporotrichosis, leishmaniasis Necrotic eschars Zygomycosis Phagedenic ulcers Buruli ulcer, amebiasis Granulomatous disorders 49 lesion. Tuberculous chancre is usually located on the face, the head and neck region, sites of predilection are the hands, and feet. cheeks, nose, ears, chin, and neck. Although lupus vulgaris Scrofuloderma, also known as tuberculosis cutis colli- usually presents as a solitary lesion, satellite or dissemi- quativa, begins as a painless subcutaneous nodule, which is nated lesions have been reported rarely.17,18 Although the called a cold abscess.6 Then, the violet-red induration bone is usually spared in lupus vulgaris, the nasal or suppurates and breaks down, forming an irregular, pus- or auricular cartilage within the affected area may be caseous material–discharging, superficial ulcer with a progressively destroyed, especially in cases left untreated granulating base and with undermined cyanotic edges. for years.19 As a result of the cartilage destruction, severe Sometimes, sinuses may develop between deep foci of the mutilations may occur.20 This mutilating character, remind- infection. Ulcers heal with retracted, cordlike, bridgelike, ing ravages of a wolf, has a significant contribution in irregular scars. Lesions are densely fibrous in some places, using the word lupus, which means “wolf,” in the name of and fluctuant or discharging in others. The most commonly the disease. Another complication of long-standing lupus affected areas are the neck, armpits, chest wall, and groin, vulgaris is the development of skin cancers, especially because the deep foci are most commonly lymph nodes and squamous cell carcinoma, and, less commonly, basal cell bones5; however, cases of facial scrofuloderma have also carcinoma and sarcomas.19,21 Facial lupus vulgaris may been reported to be due to orbital tuberculosis.7 extend to the buccal, nasal, and conjunctival mucosae. Miliary tuberculosis can cause multiple, discrete, ery- Tuberculosis of the pharynx, larynx, and middle ear may thematous papules on the skin.5 They may be capped by accompany facial lupus vulgaris.22 Again, patients with vesicles, pustules, or necrosis, so later they may become lupus vulgaris may also suffer from tuberculosis of lymph crusted. Upon removal