Cutaneous tuberculosis: diagnosis,histopathology and treatment - Part II

The evolution in the knowledge of tuberculosis'' physiopathology allowed not onlya better understanding of the immunological factors involved in the diseaseprocess, but also the development of new laboratory tests, as well as theestablishment of a histological classification that reflects the host''s abilityto contain the infectious agent. At the same time, the increasing bacilliresistance led to alterations in the basic tuberculosis treatment scheme in2009. This article critically examines laboratory and histologicalinvestigations, treatment regimens for tuberculosis and possible adversereactions to the most frequently used drugs.     

皮肤结核病研究进展

皮肤结核病由结核杆菌复合群引起,临床表现因感染途径、宿主免疫力等因素差异而呈多样性。传统的实验室诊断方法如抗酸染色直接镜检、培养、病理检查等在皮肤结核诊断和治疗中起重要作用,近年来以核酸扩增技术为代表的系列检测技术的发展为其临床精准诊断和治疗提供了重要保障本文将综述皮肤结核病的病因与发病机制、临床表现、实验室检查和治疗进展.     

Cutaneous tuberculosis

Cutaneous tuberculosis continues to be one of the most elusive and more difficult diagnoses to make for dermatologists practicing in developing countries. Not only because they have to consider a wider differential diagnosis (leishmaniasis, leprosy, actinomycosis, deep fungal infections, etc) but also because of the difficulty in obtaining a microbiological confirmation. Despite all the advances in microbiology, including sophisticated techniques such as polymerase chain reaction, the sensitivity of new methods are no better than the gold standard, that is, the isolation of Mycobacterium tuberculosum in culture. Even now, in the 21st century, we rely on methods as old as the intradermal reaction purified protein derivative (PPD) standard test and therapeutic trials, as diagnostic tools. In this situation, it is important to recognize the many clinical faces of cutaneous tuberculosis to prevent missed or delayed diagnoses.     

Cutaneous primary B-cell lymphomas: from diagnosis to treatment

Primary cutaneous B-cell lymphomas are a heterogeneous group of mature B-cells neoplasms with tropism for the skin, whose biology and clinical course differ significantly from the equivalent nodal lymphomas. The most indolent forms comprise the primary cutaneous marginal zone and follicle center B-cell lymphomas that despite the excellent prognosis have cutaneous recurrences very commonly. The most aggressive forms include the primary cutaneous large B-cell lymphomas, consisting in two major groups: the leg type, with poor prognosis, and others, the latter representing a heterogeneous group of lymphomas from which specific entities are supposed to be individualized over time, such as intravascular large B-cell lymphomas. Treatment may include surgical excision, radiotherapy, antibiotics, corticosteroids, interferon, monoclonal antibodies and chemotherapy, depending on the type of lymphoma and on the type and location of the skin lesions. In subtypes with good prognosis is contraindicated overtreatment and in those associated with a worse prognosis the recommended therapy relies on CHOP-like regimens associated with rituximab, assisted or not with local radiotherapy. We review the primary cutaneous B-cell lymphomas, remembering the diagnostic criteria, differential diagnosis, classification, and prognostic factors and presenting the available therapies.     

Cutaneous tuberculosis and malignancy

This is a report of three cases of associated tuberculous and neoplastic processes. The first is a case of lymphosarcoma complicated by cutaneous tuberculosis. The remaining two are cases of cutaneous tuberculosis complicated by squamouse cell carcinoma. Due to clinical similarity, the diagnosis of the secondary process in these cases was evoked by its failure to respond to treatment of the primary disease.     

Cutaneous tuberculosis: A great imitator

Tuberculosis (TB) is still prevalent in many developing countries and can pose a new potential threat to global health due to international migration. As an uncommon form of extrapulmonary TB, cutaneous TB is complicated in its clinical manifestation, pathogenesis, and classification. Cutaneous TB can be divided into two major categories, true cutaneous TB and tuberculid, depending on the source of infection, the route of transmission, the amount of bacteria, and the immune state of the host. Clinical manifestations may include patches and plaques (lupus vulgaris, TB verrucosa cutis), macules and papules (acute miliary TB, papulonecrotid tuberculid, lichen scrofulosorum), nodules, and abscesses (erythema induratum of Bazin, tuberculous gumma), erosions, and ulcers (tuberculous chancre, orificial TB, scrofuloderma), mimicking diverse skin diseases. Uncommon localizations such as external genitalia, unusual presentations such as nodular granulomatous phlebitis, and coexistence with other morbidities such as Behçet disease and acne inversa or hidradenitis suppurativa deserve special attention. Treatment of both true and tuberculid cutaneous TB follows the same drug regimens of the World Health Organization’s recommendation for treatment of new cases of pulmonary TB. Erythema induratum of Bazin may need longer treatment duration and adjuvants such as dapsone, potassium iodide, doxycycline, and corticosteroids to tackle inflammation. Misdiagnosis and undertreatment in daily practice are likely, and contemplation of this classic great imitator in dermatology is warranted.     

Cutaneous vasculitis: diagnosis and management

Vasculitis is histologically defined as inflammatory cell infiltration and destruction of blood vessels. Vasculitis is classified as primary (idiopathic, eg, cutaneous leukocytoclastic angiitis, Wegener's granulomatosis) or secondary, a manifestation of connective tissue diseases, infections, adverse drug eruptions, or a paraneoplastic phenomenon. Cutaneous vasculitis, manifested as urticaria, purpura, hemorrhagic vesicles, ulcers, nodules, livedo, infarcts, or digital gangrene, is a frequent and often significant component of many systemic vasculitic syndromes such as lupus or rheumatoid vasculitis and antineutrophil cytoplasmic antibody–associated primary vasculitic syndromes such as Churg-Strauss syndrome. In most instances, cutaneous vasculitis represents a self-limited, single-episode phenomenon, the treatment of which consists of general measures such as leg elevation, warming, avoidance of standing, cold temperatures and tight fitting clothing, and therapy with antihistamines, aspirin, or nonsteroidal anti-inflammatory drugs. More extensive therapy is indicated for symptomatic, recurrent, extensive, and persistent skin disease or coexistence of systemic disease. For mild recurrent or persistent disease, colchicine and dapsone are first-choice agents. Severe cutaneous and systemic disease requires more potent immunosuppression (prednisone plus azathioprine, methotrexate, cyclophosphamide, cyclosporine, or mycophenolate mofetil). In cases of refractory vasculitis, plasmapheresis and intravenous immunoglobulin are viable considerations. The new biologic therapies that work via cytokine blockade or lymphocyte depletion such as tumor α inhibitor infliximab and the anti–B-cell antibody rituximab, respectively, are showing benefit in certain settings such as Wegener's granulomatosis, antineutrophil cytoplasmic antibody–associated vasculitis, Behçet's disease, and cryoglobulinemic vasculitis.     

Cutaneous tuberculosis and pyoderma gangrenosum

A 59‐year‐old woman with multiple myeloma at stage IA exhibited recurrent pyoderma gangrenosum of 13 years’ duration. She also had a history of mitral regurgitation and cerebral infarction, but no significant family history was present. In September 1994, she noted a painful erythematous papule on her left foot, which was treated with a topical injection of triamcinolone. It responded well to this treatment at the time, but a similar eruption developed in the same place in February 1995, and enlarged to form an irregularly shaped, punched‐out ulcer with surrounding infiltrative erythema despite topical treatment ( Fig. 1 ). Further, since November 1994, she had noted pain in the right dorsal foot.

Figure 1 Open in figure viewer PowerPoint Necrotic ulcer with an elevated purulent border and pustules on the left foot     

Cutaneous tuberculosis and squamous-cell carcinoma

The incidence of all forms of cutaneous tuberculosis, including lupus vulgaris (the most common form) decreased progressively in developed countries during the twentieth century, this change being attributed to improved living standards and specific therapy. Despite the decrease in cutaneous tuberculosis, some cases are still found and correct diagnosis and management are fundamental, both for the patients and for public health. Long lasting, misdiagnosed or untreated cutaneous tuberculosis may lead to different forms of cancer. This case report involves a 74-year old male farmer with lupus vulgaris on his face. During anti-tuberculosis treatment he developed a tumor on his forehead, which was histologically confirmed as a squamous cell carcinoma.     

Cutaneous sarcoidosis: differential diagnosis

Sarcoidosis is a multisystem disease with cutaneous lesions present in 20%-35% of patients. Given the wide variability of clinical manifestations, it is one of the "great imitators," making it necessary to consider clinical, epidemiological, radiographic, laboratory, and histopathological criteria to make the diagnosis. Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of noncaseating granulomas on histologic studies. Specific lesions include maculopapules, plaques, nodules, lupus pernio, scar infiltration, alopecia, ulcerative lesions, and hypopigmentation among others. Nail, mucosal, and childhood sarcoidosis represent a distinct subset of the disease process. The most common nonspecific lesion is erythema nodosum. Others include calcifications, prurigo, erythema multiforme, nail clubbing, and Sweet syndrome. The importance of considering cutaneous sarcoidosis in the clinical differential diagnosis of a given skin lesion relies on the association with systemic involvement and the convenience of the skin as a tissue source for histologic analysis.     

Cutaneous manifestations of tuberculosis

Cutaneous involvement is a rare manifestation of tuberculosis (TB). The correct diagnosis is often significantly delayed because cutaneous TB is not routinely considered in the differential diagnosis or because investigations fail to reveal the presence of Mycobacterium tuberculosis. The clinical features of cutaneous TB are diverse, and result from exogenous and endogenous spread of M. tuberculosis and from immune-mediated mechanisms. The recognition of cutaneous TB is important, as the diagnosis is frequently overlooked resulting in delayed treatment.     

Cutaneous lupus erythematosus: diagnosis and management

Cutaneous lupus erythematosus (CLE) includes a variety of lupus erythematosus (LE)-specific skin lesions that are subdivided into three categories - chronic CLE (CCLE), subacute CLE (SCLE) and acute CLE (ACLE) - based on clinical morphology, average duration of skin lesions and routine histopathologic examination. This paper describes our personal experience in the management of CLE over the last 30 years, with details on preferential therapeutic options related to clinical, histologic and immunopathologic aspects of each clinical subset of the disease. Effective sunscreening and sun protection are considered the first rule in the management of CLE because of the high degree of photosensitivity of the disease. Antimalarial agents are crucial in the treatment of CLE and are the first-line systemic agents, particularly in discoid LE (DLE) and SCLE. Dapsone is the drug of choice for bullous systemic LE (BSLE) as well as for LE in small dermal vessels (e.g. leukocytoclastic vasculitis). Retinoids, known as second-line drugs for systemic therapy, are sometimes used to treat chronic forms of CLE and are particularly successful in treating hypertrophic LE. Systemic immunosuppressive agents are required to manage the underlying systemic LE disease activity in patients with ACLE. These drugs, especially azathioprine, methotrexate, cyclophosphamide and cyclosporine, together with corticosteroids, constitute third-line systemic therapy of CLE. In our experience, oral prednisone or parenteral 'pulsed' methylprednisolone are useful in exacerbations of disease activity. Thalidomide provides one of the most useful therapeutic alternatives for chronic refractory DLE, although its distribution is limited to a few countries because of the risk of teratogenicity and polyneuropathy. However, medical treatment with local corticosteroids remains the mainstay of CLE treatment, especially for DLE. Patient education regarding the disease is also important in the management of CLE, because it helps relieve undue anxiety and to recruit the patient as an active participant in the treatment regimen.     

Cutaneous tuberculosis and phlyctenular keratoconjunctivitis: a forgotten association

Cutaneous tuberculosis may be associated with concurrent systemic foci in the body such as lung, lymph node, bone or CNS. Phlyctenular keratoconjunctivitis (PKC) is a manifestation of immunological response to a variety of antigens in the eye, tubercular focus (evident or occult) being the commonest in India. Reports in the existing literature have shown lungs and lymph nodes to be the predominant underlying focus associated with PKC, whereas cutaneous tuberculosis has seldom been found in this situation. We report this forgotten association in two children with cutaneous tuberculosis, one each with lupus vulgaris and scrofuloderma, who also had PKC. Interestingly, one of the cases also had simultaneous lichen scrofulosorum, which is also an immunological response to tubercular antigen and manifests in the skin, thus showing immunological manifestation in two different organ systems along with cutaneous focus of tuberculosis.     

Cutaneous sarcoidosis: Prognosis and treatment

The physician who has made a diagnosis of cutaneous sarcoidosis is faced with three basic questions: (1) Are there lesions in organs other than the skin? (2) Should the patient be given treatment? (3) What will the final outcome of the disease be?

Cutaneous sarcoidosis can be a great imitator of other skin diseases with a wide spectrum of clinical manifestations ranging from small asymptomatic cutaneous lesions that fade spontaneously without scarring, to widespread skin lesions and disease in many organ systems. The latter may be associated with severe symptoms such as pulmonary insufficiency or life-threatening biochemical abnormalities. Approximately two thirds of all patients recover completely or with a minimum of residual changes, while 2–5% of sarcoidosis patients die from the disease.^1,2

It is therefore of interest to review the literature that deals with the course and prognosis of sarcoidosis. It is also important to deal with the association of cutaneous sarcoidosis and other types of sarcoidosis in order to provide the dermatologist with a basis for his or her decision about whether treatment should, in fact, be instituted.