Leprosy
Leprosy is a chronic granulomatous mycobacterial disease that can affect the peripheral nerves, skin, eyes and testes. The causative agent, Mycobacterium leprae, multiplies very slowly and is not highly contagious. It is transmitted by droplets or skin contact to people in prolonged and close contact with untreated bacillary patients. Symptoms do not appear immediately after the microorganism enters the body. The incubation period averages 5 years (2–20 years). The variable and long incubation period makes diagnosis difficult. Although the incidence of leprosy has decreased today, it remains an important public health problem in endemic countries. According to World Health Organization (WHO) estimates, the global prevalence of leprosy is 11 million, with most cases in South and South-East Asia, Africa and Latin America. Since multidrug therapy consisting of dapsone, rifampicin and clofazimine was introduced, the prevalence rate has fallen by about 85% and leprosy has been eliminated in 98 countries. However, the number of new cases, estimated at around 600,000–700,000 a year, has not fallen significantly despite multidrug therapy.
Although leprosy is not a major health problem in Turkey, it has always existed throughout history. Leprosy control work continues on the principle of a multifaceted approach to the patient, in the form of anti-leprosy treatment, physical and social rehabilitation, surgery, and services addressing and solving health problems other than leprosy. In Turkey, three inpatient centres provide services, the largest in Elazığ and the others in Istanbul and Ankara. As of 2000, there were known to be 2,592 patients in Turkey (<1/25,000), 917 of them women.
Leprosy is a disease that leaves the individual weak and frail. The disease is characterised by a multibacillary form with predominant skin findings, lepromatous leprosy, and a paucibacillary form with predominant peripheral nerve involvement, tuberculoid leprosy. Between these two forms, borderline forms without clear limits can appear with many different clinical pictures. In the tuberculoid form the clinical course is milder and patients have strong cell-mediated immunity. This form has low infectivity. It is characterised by hypopigmented macules on the skin. Peripheral nerve damage with complete loss of sensation and thickening of the nerves may be seen. It may show reactivity to the lepromin test. The lepromatous form is characterised by shapeless skin lesions, nodules, plaques, thickened dermis and involvement of the nasal mucosa. These patients have a strong antibody response, but there is a marked defect in the cell-mediated immune response to M. leprae antigens. This is the most contagious form of leprosy. There are many erythematous macules, papules or nodules, widespread tissue destruction (nasal cartilage, bone, ears, etc.) and widespread nerve involvement with regional loss of sensation. There is no nerve thickening.
The general clinical signs can be summarised as follows:
Lesions on the skin in the form of one or more raised plaques that are hairless, do not sweat, are scaly and always have a sensory deficit,
Patches anywhere on the body that are lighter than the skin, oval or round, not raised, cause no complaints, are not scaly and sometimes show a slight sensory deficit,
In children and young people, persistent nasal congestion and frequently recurring nosebleeds,
Reduced sensation in certain areas, especially the inner surface of the forearm,
Inward curling of the fourth and fifth fingers of the hand and the start of wasting of the palm muscles,
Thickening and tenderness of the nerves of the arms and legs,
Loss of the eyebrows,
Bacillary nodules on many parts of the body,
Oedema of the face, with the skin of the forehead and the ears filled with purplish, raised, hard nodules,
Scars on the knees and elbows,
Inability to close the lower eyelids.
Tuberculoid Leprosy
In a person with high cell-mediated immunity, the bacillus reaching the Schwann cell multiplies only in that nerve. A tuberculoid granuloma formed by epithelioid histiocytes and giant cells in the nerve leads to thickening, pain, loss of sensation and muscle wasting. The thickening of the nerve can be seen and palpated. The type of leprosy that develops in this way is tuberculoid leprosy.
In tuberculoid leprosy, usually one or at most two or three nerves are affected. The nerves of superficial and cool areas (face, neck, arms and legs) are most often involved. In the areas supplied by these nerves, the sensations of pain, touch, heat and cold are lost.
The skin sign is one or several plaques, up to 30 cm in diameter, on the skin of the area near the affected nerve. This plaque is hypopigmented or erythematous, sometimes slightly scaly, oval or round, sharply demarcated, slightly raised and infiltrated. Bullae and ulceration may develop in the lesions. The plaque has a sensory deficit, is dry, does not sweat and has lost its hair.
There are no bacilli in the lesion or in unaffected skin, and the lepromin test is strongly positive. Histopathology shows a tuberculoid granuloma made up of epithelioid cells surrounded by lymphocytes. Langhans-type giant cells are present. In the peripheral nerve, a granulomatous reaction sparing the perineurium is seen.
Borderline Leprosy
Borderline leprosy develops when immunity is moderate. If the immune response is close to tuberculoid leprosy, borderline tuberculoid leprosy develops; if it is close to lepromatous leprosy, borderline lepromatous leprosy; and if it is exactly in the middle, mid-borderline leprosy.
The borderline types of leprosy are not stable and can easily change type. If the disease is not treated it shifts towards the lepromatous end; if it is treated it shifts towards the tuberculoid end.
In borderline tuberculoid leprosy there are numerous plaques. The plaques are asymmetrically located, less infiltrated than in TT, with less distinct borders and satellite lesions around them. More than one nerve is involved asymmetrically; the nerves are thick and painful. Sweating is reduced in the lesions, there is a sensory deficit and there are no bacilli. The lepromin test is weakly positive. Histopathology shows epithelioid cells, occasional giant cells and moderate lymphocytic infiltration.
In borderline lepromatous leprosy there are macules, papules, nodules and plaques; they resemble those of lepromatous leprosy but are not symmetrical. It can be distinguished clinically from lepromatous leprosy by the absence of mucosal involvement and of eyebrow and eyelash loss. Almost all peripheral nerves are involved, but there is no pain. There is no sensory deficit in the lesions; bacilli are abundant. The lepromin test is negative. Histopathology shows an infiltrate made up mostly of macrophages. Lymphocytes are sparse and form clusters in the centre of the granuloma.
Mid-borderline leprosy is a rare type at the very centre of the borderline spectrum that easily shifts to BT or BL. The lesions are macules, papules, plaques or various combinations of these. The lesions tend to be symmetrically located. Peripheral nerve involvement varies. Bacilli are found in the lesions, and the lepromin test may be negative or positive.
The most common types of leprosy in Turkey are BL and LL.
Lepromatous Leprosy
Lepromatous leprosy develops when the bacillus reaching the Schwann cell multiplies freely in a person with impaired cell-mediated immunity and spreads via the blood, lymph and contiguous tissues to the skin and internal organs. At the beginning the disease has two signs, which are missed unless asked about: nasal symptoms and local oedema of the hands and feet. Nasal symptoms are present in most cases; these are nasal congestion, crusting in the nose and blood-stained nasal discharge. Oedema around the ankles is the other important finding. This sign mostly worsens towards the evening and subsides with rest.
In lepromatous leprosy the lesions are located symmetrically on the exposed areas of the body (face, limbs) and the trunk. The immune zones (scalp, armpits, groin, perineum, midline of the back) are not involved. The initial lesions are numerous small, ill-defined, hypo- or hyperpigmented or erythematous macules with no or only slight sensory deficit, and sweating and hair growth are normal. At this stage there is no nerve thickening. Later, papules, nodules (lepromas) and plaques appear. The lesions have a sensory deficit, sweating has stopped and the hair has fallen out. All the peripheral nerves thicken, and symmetrical sensory deficits develop in a glove-and-stocking distribution on the hands and feet.
The raised lepromas on the face and the depth of the furrows create an appearance called lion face (facies leonina). Facial hair loss develops; at first the eyebrows fall out from the outer ends (sign d’Omnibus), and later all the eyebrows and eyelashes are lost (madarosis); the scalp is usually unaffected.
There are abundant bacilli in the lesions and in unaffected skin, and the lepromin test is negative. Histopathology shows an infiltrate made up mostly of macrophages in the mid and deep dermis, with sparse lymphocytes.
If the patient remains untreated, the eyes, reticuloendothelial system, bones, testes and other organs become diseased, and deformities and complications arise.
Erythema Nodosum
Erythema nodosum is a hypersensitivity reaction characterised by symmetrical, inflammatory nodular lesions that can regress spontaneously, usually located on the extensor surfaces of the lower limbs. It is most common between the ages of 20 and 30 and in women, F>M: 4/1. It is thought to arise through the formation of immune complexes against a triggering agent.
Causes of erythema nodosum
In 35–50% of patients no cause is found and it is considered idiopathic. Streptococcal infections are the most common cause; it begins on average 3 weeks after the infection. In Behçet’s disease it is usually migratory in character. Medicines: it may be caused by oral contraceptives, sulphonamides, bromides, iodine, gold and antibiotics. It may be due to tuberculosis or sarcoidosis. Leprosy: the lesions, called ’’erythema nodosum leprosum’’, may be widespread and ulcerated. It may also be caused by viral, chlamydial and bacterial diseases, deep fungal diseases, malignancies, collagen tissue diseases (especially SLE), inflammatory bowel diseases and pregnancy.
Erythema Nodosum: Clinical Features
It begins with non-specific prodromal symptoms: fatigue, fever, arthralgia (especially in the knees), morning stiffness and headache. It takes the form of painful, symmetrical, firm, locally warm, erythematous nodules 1–10 cm in diameter, most often located on the front of the shins. It may also occur on the face, arms and thighs. The number of nodules varies. Recurrences are common, depending on the underlying cause. At first the nodules are bright red. They then become livid-purple and yellowish-green. Ulceration is not seen. They last 3–6 weeks and regress without scarring, leaving post-inflammatory hyperpigmentation.
Cutaneous Tuberculosis
Tuberculosis has shown a global increase over the last 20 years. In the USA and European countries, the increase in the number of people migrating from countries with a high prevalence of tuberculosis, the growth of communal living units such as homeless shelters and prisons, the rapidly increasing numbers of AIDS cases and drug-resistant tuberculosis strains, and the more widespread use of immunosuppressive medicines are held responsible for the rise in tuberculosis incidence. Tuberculosis is still a major problem for developing countries, where it is estimated that 30–60% of adults are infected with Mycobacterium (M.) tuberculosis. Compared with tuberculosis of other organs, cutaneous tuberculosis is relatively rare. A study carried out at a tuberculosis dispensary in Turkey found that, of 1,130 tuberculosis cases diagnosed and treated over a 10-year period, 234 had extrapulmonary tuberculosis, while only 5 (2.2%) were diagnosed with cutaneous tuberculosis. Another study reported cutaneous tuberculosis in 13 (3.51%) of 370 patients with tuberculosis of the lungs and/or other organs.
The incidence of cutaneous tuberculosis is reported to vary between 0.02% and 0.59% depending on the country (5-7). It is thought that the general increase in tuberculosis will also lead to cases of cutaneous tuberculosis being seen more often. Cutaneous tuberculosis is caused by M. tuberculosis, M. bovis and, rarely, the attenuated strain of M. bovis, Bacillus Calmette-Guérin (BCG). The bacilli reach the skin from outside the body (exogenous spread) or from a focus of tuberculosis inside the body (endogenous spread). Although there is no ideal method of classifying cutaneous tuberculosis, it is appropriate to assess cases in 4 main groups according to the mechanisms by which the disease arises.
Lupus Vulgaris
A chronic and progressive type of cutaneous tuberculosis that develops in patients who have previously encountered the bacillus and have strong immunity to tuberculosis and a positive PPD. Although lesions may be seen at the site of inoculation or BCG vaccination and on scrofuloderma scars, they most often develop in areas distant from the initial focus of infection. The disease typically presents as a single plaque made up of clustered and merging red-brown, translucent, soft papules (lupomas). When a glass slide is pressed on the plaque, the erythema fades, leaving a yellowish-brown colour reminiscent of apple jelly. While the papules heal in one area leaving atrophic scars, new lesions develop in another area. The development of new lesions on scars is one of the characteristic findings of lupus vulgaris. The lesions are mainly located over cartilage such as the nose and ears, on the cheeks and, less often, on the arms, legs and trunk. Owing to scarring, serious sequelae such as ectropion, eclabium, microstomia, near-total loss of nasal tissue, joint contractures and elephantiasis may arise. Histopathological examination shows typical granulomas (tubercles) with very little caseation necrosis, containing Langhans-type giant cells and epithelioid cells; bacilli are few. The lesions progress slowly and, if untreated, may last a lifetime. In 10% of cases squamous cell carcinomas develop on the scars.
Tuberculosis Verrucosa Cutis
It arises when M. tuberculosis or M. bovis enters the skin from outside in a patient who has previously encountered the bacillus and has moderate or strong immunity (reinfection tuberculosis). The PPD test is strongly positive. Pathologists, laboratory workers, farmers, vets and butchers are among the high-risk occupational groups. The disease, which usually presents with a single lesion, is most often located on areas exposed to trauma such as the hands and lower limbs. Beginning as a small purplish or brownish-red papule, the lesion becomes hyperkeratotic, resembling a common wart, and gradually enlarges. On the surface of the plaque, surrounded by a purple inflammatory halo, papillary projections and fissures from which pus and keratinised material ooze with light pressure may be seen. Regional lymphadenopathy is not seen unless there is secondary bacterial infection.
On histopathological examination, pseudoepitheliomatous hyperplasia is prominent in addition to suppurative and granulomatous inflammation in the upper and mid dermis. The course of the disease varies; the lesion may persist for years or heal spontaneously, leaving atrophic scars.
Scrofuloderma
It develops as a result of contiguous spread of the bacillus to the skin, most often from an underlying tuberculous lymphadenitis and sometimes from tuberculous bones or joints. It is most often seen on the sides of the neck, under the jaw, over the sternum, and in the armpits and groin. The lesions begin as firm, painless nodules under the skin, covered by normal skin. The nodule gradually softens and becomes fluctuant, opens onto the skin, and a watery, purulent or caseous material drains from the fistula openings. At this stage the skin over the lesion may become purplish-red, but there is usually no local warmth (cold abscess). As it opens onto the skin, sinuses or irregularly shaped, undermined ulcers with a base covered in granulation tissue and surrounded by a violaceous erythematous ring are formed. The PPD test is usually positive. If untreated, scrofuloderma can last for years and heals with scar tissue forming cords and bridges, which is characteristic of the disease. Histopathological examination shows a centre made up of polymorphonuclear leucocytes and debris, surrounded by typical granulomatous inflammation.
Metastatic Tuberculous Abscess
This type, also called tuberculous gumma, develops when immunity is weakened, as a result of bacilli reaching the skin via the bloodstream from a primary focus. It is seen mostly in malnourished children, people with AIDS and those with immunosuppression from other causes. Painless, fluctuant subcutaneous abscesses develop on the head, trunk or limbs, and when they open, fistula openings and ulcers similar to scrofuloderma appear. PPD is usually positive.
Tuberculids
These are a group of symmetrically distributed skin eruptions that accompany an underlying focus of tuberculosis and are probably due to hypersensitivity to the bacillus. The common features of tuberculids are:
- the general condition of the patients is good
- the PPD test is positive
- there is usually inactive tuberculosis of the internal organs or lymph nodes
- direct smears and cultures from the skin lesion usually fail to show the bacillus
- the lesions respond to tuberculosis treatment.
However, in recent years the demonstration of mycobacterial DNA in the lesions by PCR has given rise to the view that these lesions develop through blood-borne spread of the bacillus in people with strong immunity to tuberculosis.
Lichen Scrofulosorum
It is seen particularly in children with tuberculosis of the bones, lungs and lymph glands. It consists of asymptomatic, clustered, yellow-pink lichenoid papules 1–2 mm in diameter, mainly located on the trunk, which may have scales or superficial vesicles on top. After a course of several weeks it usually heals spontaneously without scarring. It also responds well to anti-tuberculosis treatment.
The demonstration (Ziehl-Neelsen staining, PCR) and culture of the bacillus are essential in the diagnosis of cutaneous tuberculosis. However, because the bacilli are few, demonstrating them is often not possible; for this reason clinical and histopathological findings, and sometimes even the response to anti-tuberculosis treatment, guide the diagnosis. Since most cases of cutaneous tuberculosis have an overt, active or latent systemic infection, treatment is generally similar to that given for tuberculosis of other organs. In addition to multidrug anti-tuberculosis treatment, physical destructive methods such as surgical excision, cryotherapy and electrocautery can also be used.
Erythema Induratum of Bazin
A chronic disease that mainly affects middle-aged women and accompanies past or active tuberculosis. It begins with tender, painful, erythematous or violaceous subcutaneous nodules or plaques 1–2 cm in diameter, most often on the calves and less often on the buttocks, thighs and arms. After persisting for months, the lesions regress spontaneously or ulcerate. The lesions, which tend to recur, often heal leaving scars. The disease, which shows features of lobular panniculitis with vasculitis, is thought to be a vascular reaction developing in the subcutaneous fat as a result of hypersensitivity.
Lupus Miliaris Disseminatus Faciei
Lupus miliaris disseminatus faciei (LMDF) is a granulomatous disease of the face of unknown cause, seen in both sexes and mostly in young adults. Clinically it is characterised by numerous red papules appearing symmetrically on the face. Although most lesions regress within a few years without treatment, they leave scars that cause permanent disfigurement of the face. If the disease is detected early and treatment is started, it can heal without scarring.