Lupus vulgaris: causes, symptoms, diagnosis, and treatment

Lupus vulgaris, also known as tuberculosis luposa, is a common type of cutaneous tuberculosis characterized by many apple jelly nodules and plaques, with irregular expansion, scar formation, and tissue destruction, persisting for many years.


Causes

Lupus vulgaris is secondary cutaneous tuberculosis in persons who have been previously infected with mycobacterium tuberculosis and have been sensitized and are highly sensitive to tuberculin purified protein derivative. Mycobacterium tuberculosis can invade the skin through skin breaches. Lupus vulgaris can be caused by the spread from the ruptured lymph nodes, bone, and joint tuberculosis lesions, or through lymphatic vessels. Lupus vulgaris can result from dissemination of visceral tuberculosis lesions through bloodstream. Few cases occur in the BCG vaccination site. Therefore, it is considered that after the vaccination of BCG, if granulation tissue occurring at the vaccination site cannot be regressed for a long time, follow-up should be performed.

In addition, nutrition, living conditions, health status, and personal resistance are associated with the occurrence and development of lupus vulgaris.


Signs and Symptoms

The basic lesions are pinhead sized to pea sized, reddish brown to brown, translucent, slightly raised nodules, with soft texture, with thin and tender surface that is easily penetrated by a probe. In diascopy, the local congestion is reduced, and the nodule is obviously pale yellow or yellowish brown and is similar to apple jelly, so it is also known as apple jelly nodule. Sometimes many nodules merge with each other to form a large reddish brown infiltrated lesion, covered by large leafy scales, with a diameter up to 10 - 20cm, with uneven surface, with soft texture.

In the long duration, some lesions spontaneously heal, forming scars, and some nodules are often ruptured, forming ulcers. Ulcers are only part of the lesion initially, and the whole lesion can be ulcerated in the future. Most ulcers are superficial, round or irregular, with surface composed of reddish brown granulation tissue, with little thin pus, leaving dirty brown thick crusts after dryness of pus. The edges of the ulcer are irregular, soft, dark red, and undermined. In the process of development, the center or one side of the ulcer is cured after scarring, but the edges or the other side is continuously expanding outward, which can form a large piece of lesion, and can also form annular, arc shaped, or creeping lesions. The tissue is severely destructed, and rugged funicular scars are formed after healing. In severe patients, cicatricial contraction may cause deformity or dysfunction. Another feature of lupus vulgaris is that new nodules can occur in the scars, forming ulcers after rupture, so that the disease often persists for decades.

In addition to the typical lesions, due to the different reactivity of patients, there are more clinical types:

  • Lupus planus is characterized by smooth surfaces, with or without few scales, infiltrating patches composed of lupus nodules, and flattened atrophic scars after healing.
  • Hypertrophic lupus vulgaris, including nodular lupus, lupus tumidus, lupus verrucosus, and lupus papillaris, is manifested by densely fused nodules, raised and obvious infiltrative masses, or different sized papillary proliferations.
  • Lupus exulcerans often presents with large areas of ulcers resulting from ruptured nodules or is secondary to tuberculosis of lymph nodes, bones, or other tissues under the skin.
  • Lupus disseminatus is caused by dissemination of mycobacterium tuberculosis from internal focal tuberculosis lesions through bloodstream. The disease can be seen in children after acute infectious diseases such as measles or scarlet fever. Numerous scattered small patches composed of nodules suddenly occur, without fusion.

The predilection site of lupus vulgaris is the face, accounting for more than 50%, followed by extremities, buttocks, and neck. Facial lupus vulgaris often causes tissue destruction and destroyed face, such as nasal cartilage, nasal wing destruction, and beaked nose. Sometimes the nose is completely destroyed, only the posterior nasal septum and the nasal turbinate are visible. The auricle may be destructed and only the earhole is visible. The destruction of the cheek and eyelid skin and cicatricial contraction can cause ectropion and lagopthalmus, leading to conjunctivitis, keratohelcosis, and even blindness. Limb and neck lesions can cause contracted deformity due to cicatricial contraction. Sometimes muscles, tendons, or bones can be destroyed, or abscission of digits may occur, resulting in reduction deformity.

Lupus vulgaris also often invades the mucosa. Mucosal lesions can be primary, or extended from facial lupus, more common in the nasal mucosa and perioral area. Nasal mucosal lesions can involve the dacryocyst and even the conjunctiva along the nasolacrimal duct and can extend back to the nasopharynx and the anterior hard palate through the anterior palatine foramen. Pharyngeal lesions can spread to the middle ear through the eustachian tube. Mucosal lupus can occur in the entire oral mucosa and lips, but due to mucous membrane moisture and other bacterial contamination, mucosal lupus is manifested by a slightly raised, greyish white granulation patch, with granular surface, sometimes accompanied by tiny ulcers, and scarring on the surface. Swelling and ulcers can occur in the gingivae, the tooth can also fall off, occasionally papillary hypertrophy or painful cracks can occur if the tongue is invaded. Oral mucosal lesions and eating disorders can result in malnutrition.

Obvious subjective symptoms are absent in lupus vulgaris, pain may be present in secondary infections. If not accompanied by other tuberculosis, systemic symptoms are mild. The reinfection of tuberculosis generally does not involve local lymph nodes.

Lupus vulgaris often occur in children or juveniles, more than a half of patients are aged less than 10 years, and about 80% of patients are aged less than 20 years.


Complications

Secondary infections: patients with lupus vulgaris often have septic infections such as impetigo, furuncles, and erysipelas.

Elephantiasis: lupus vulgaris may be complicated by lymphangitis or lymphadenitis, and repeated attacks result in destruction of lymphatic vessels or lymph nodes and lymphatic obstruction, leading to elephantiasis.

Other tuberculosis: patients with lupus vulgaris can have tuberculosis in other organs. For example, it is estimated that about 25% of patients may have active pulmonary tuberculosis, and 30% of patients may have bone tuberculosis.

Skin cancer: squamous cell carcinoma can be complicated in the long-term lupus lesions, and the incidence rate is about 1% - 2%.


Histopathology

The pathological changes of lupus vulgaris mainly occur in the superficial layer of the dermis, but also spread to the deep dermis and even the subcutaneous tissue, and can cause destruction of the skin appendages.

Pathological infiltration is mainly tuberculous nodules, and nodules with caseous necrosis are rare and mild even if present. Infiltrating cells are mainly lymphocytes, epithelioid cells, and giant cells. Although giant cells are usually Langhans giant cells with marginally arranged nuclei, some are multinucleated giant cells with irregularly arranged nuclei. The earlier the lesion is, the more lymphocytes are, and they are surrounding the infiltrating focus. Epithelioid cells and Langhans giant cells predominate when the lesion has persisted for a long time, and epithelioid cells are mostly clustered concentrically or irregularly arranged. Blood vessel is absent in the infiltrating focus, but collagen fibrosis is present. Finally, the elastic fiber can also be degenerated and destroyed. When the lesion heals, the reticular fibers at the margin are densified and collagenized, and extensive fibrosis is present. Elastic fibers cannot be recovered.

Epidermal changes are secondary, and in some cases, acanthosis, hyperkeratosis or papillomatosis, even pseudoepitheliomatous hyperplasia, and occasionally squamous cell carcinoma are present. However, in some cases, the epidermis may be atrophied and thinned due to compression caused by infiltration in the dermis, and even ruptured, forming ulcers. Suppuration may be caused by secondary infection, so that many neutrophils, eosinophils, and other pyogenic bacteria are found in the infiltration.

In histopathology, mycobacterium tuberculosis may be present but not easily found and even culture and animal inoculation cannot be successful.


Diagnosis

On the basis of features of lupus vulgaris, such as occurrence mainly in children, apple jelly nodules, scars after healing, and new nodules in the scars, and tuberculous infiltration in histopathology, diagnosis is not difficult.

Differential diagnosis

Sarcoidosis is with firmer nodules, with infiltration generally not ruptured, with negative results in tuberculin test.

Nodular syphilid is with quickly developing copper red nodules, with or without creeping arrangement, with texture as hard as cartilage. The nodules are often ruptured, and excavating ulcers are present, leaving scars after healing. Positive results in serological test of syphilis are present. The pathological changes are mainly plasma cell infiltration and vascular changes.

Discoid lupus erythematosus is with butterfly erythema often symmetrically distributed in the nose and cheeks, without nodules and ulcers, with adhesive scales on the erythema, with follicular keratotic plug attached to the bottom.

Deep mycosis is with nodules often ruptured, forming scars. Positive results in fungal culture are present. Pathogens can be found in histopathology.

Tuberculoid leprosy is with slightly harder nodules, and sensory disturbances in the affected area are its feature. Thickened peripheral nerves and numbness and malformation of extremities are present. Trophic ulcers may be visible.


Treatment

Small pieces of lesions can be scraped under local anesthesia and postoperative compression can be used to stop bleeding. For a small range of skin lesions, annular subcutaneous injection of 1% procaine solution plus 2.5% isoniazid solution to the surrounding of skin lesion can be performed, or topical 5% isoniazid ointment can be applied. After treatment, if the nodule does not regress for a long time, local diathermy or topical carbolic acid under local anesthesia can be applied.

Standard anti-tuberculosis treatment regimen should be performed.

First-line anti-tuberculosis drugs include isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), and ethambutol (EMB). These drugs should be treated in combination.

Second-line anti-tuberculosis drugs are often used in drug-resistant tuberculosis patients or patients unable to tolerate first-line drugs, mainly including aminoglycosides and fluoroquinolones, such as streptomycin, kanamycin, amikacin, capreomycin, levofloxacin, and moxifloxacin. Aminoglycosides are only for parenteral use.

Other second-line drugs include ethionamide, cycloserine, and para-aminosalicylic acid, with anti-tuberculosis effect weaker than first-line drugs, with strong toxicity, but effective against drug-resistant tuberculosis.

Bedaquiline, delamanid, and sutezolid are new anti-tuberculosis drugs and are usually reserved for extensively drug-resistant tuberculosis, or patients unable to tolerate other second-line drugs.