NODULAR LESIONS OF THE SKIN

A cutaneous nodule is a circumscribed relief of the skin, which persists for weeks. In this chapter are included the skin disorders characterized by nodular infiltration of the dermis, both of the inflammatory (granuloma) and proliferative type. We will initially treat the inflammatory or granulomatous nodular lesions, which are caused by infectious agents -viruses, bacteria and fungi-, by infestation -leishmaniasis, scabies and tick bite, by other agents -post-traumatic granuloma and granuloma gluteale infantum- or by not defined causes -annular granuloma, granuloma faciale and sarcoidosis-.

Chronic granulomatous disease

We are starting from chronic granulomatous disease (CGD). Although caused by infectious agents, CGD is determined by an inherited deficiency of bactericidal function of phagocytes.
Chronic granulomatous disease is usually transmitted by a recessive x-linked trait. Therefore, it prevails in the male born to a female carrier of the gene defect. The gene has been mapped to the Xp21.1 region of the X chromosome. There are also forms transmitted with an autosomal recessive trait. The consequent gene defect consists in the lack of a b-cytochrome. The latter plays a significant role in oxidase system, which is responsible for the burst of respiratory oxidative activity of phagocytes. The defect is present in the polymorphonuclear leukocytes, eosinophils and monocytes. The bacterial phagocytosis is usually associated with a burst of the oxidative respiratory activity, which release hydrogen peroxide and unstable intermediate radicals with bactericidal activity such as singlet oxigen hydroxil radicals. Hydrogen peroxide combining with chloride and iodide ions, gives raise to oxyhalides, which play a significant role in the bactericidal activity. The reaction is catalysed by myeloperoxidase.
The accumulation of living bacteria in the phagocytes leads to the formation of granulomas in the skin, lymph nodes, lungs, liver, intestine and bone marrow.
The easiest laboratory diagnosis is made by the nitroblue tetrazolium dye test. The latter is based on the ability of polymorphonuclear leukocytes of reducing during the phagocytosis the oxidate and colorless tetrazolium nitroblue to blue formazan.
From a clinical point of view, the onset of the disorder is early, usually in the first two years, and characterized by neonatal pustulosis and nonspecific, impetiginized, periorificial lesions, usually on the face (Fig. 725).

		Folliculitis of the scalp, perianal abscesses and suppurating perionyxis are often present. All these infectious disorders are due to Staphylococcus aureus or opportunistic bacteria such as Nocardia, Legionella or Aspergilli. Besides the skin lesions, which often are the first sign of CGD, are also present short stature, recurrent pneumonia with its characteristic radiological finding of encapsulating pneumonia and gastrointestinal infections, with characteristic obstructive granulomatous lesions. The prognosis is variable and positively influenced by a continuous antibiotic (trimethoprim-sulphamethoxazole) and antimycotic treatment and by a careful cutaneous antisepsis. Interferon gamma and bone marrow transplantation can be also useful.
Fig. 725: Chronic granulomatous disease with nodular lesions of the face.

Granulomatous virus infections Some virus infections can be sometimes characterized by a granulomatous appearance, due to coexisting particular disorders. Herpes simplex in subjects suffering from leukemia can be for example characterized by a granulomatous appearance (Fig. 726, 727). Milkers’ nodules are due to a pox virus. The latter is responsible for cow’s mastitis. We are dealing with a professional disease affecting milkers. The disease is characterized by an inflammatory granulomatous lesion of the hands (Fig. 728), which later undergoes hemorrhagic necrosis and spontaneously regresses.
		Fig. 726: Granulomatous herpes simplex in a subject with leukemia.

Granulomatous bacterial diseases

The great chronic infectious diseases played a significant role in the history of dermatology. Although less frequent and fightening as compared with the past, these disorders are still responsible for a prejudicial interpretation of the cutaneous lesions, especially of those lesions persisting for a long time on exposed and visible sites. In the past these disease were characterized by contagious lesions in exposed areas and by a severe, sometimes lethal prognosis. Today still persists a prejudicial fear of these lesions, which extended in the popular phantasy to all the dermatological lesions persisting on exposed sites. This is why every persisting and visible skin lesion raises in people who observe it the fear of contagion and therefore repulsion towards the affected subject. In their turn the affected people, besides suffering from the variable consequences of the dermatological disorders, must also face this further sufference, namely the feeling of being prejudicially rejected, only because of a visible and persisting skin lesion, even though the latter is not contagious. Therefore, it is not strange that a persisting and visible shin disorder is considered a misfortune, both in religious myth -as in the case of Job- and art.
As important consequence of this prejudice, physicians who diagnose a non contagious skin disorder, should with their words and gestures reassure the patient and his/her parents that they are not dealing with a contagious disease, even though the relevant question is not raised.

Fig. 730: Scrofuloderma with granuloma- tous lesions and with evident submandibular adenopathy.

Cutaneous tubercolosis. Scrofuloderma (Fig. 730) is most frequently diagnosed in childhood in the developed countries. We are dealing with a secondary tuberculosis, in which the skin is affected by contiguity from an underlying tubercular lesion, usually an affected cervical lymph node. The characteristic lesion is a 2-4 cm in size, inflammatory, reddish, tense (Fig. 731) nodule, which progressively gets more tense till being ulcerated (Fig. 732). The underlying lymph node is not always clinically evident. After the ulceration fistolous passages develop, often communicating each other and exudating. Later on, the reparative fibrous process starts, eventually leading to an often disfigurating, irregular scar.

The pathological examination, which is rarely performed in this disorder, initially shows a typical tubercular granuloma, consisting of epithelioid cells with Langhans giant cells in the middle and lymphomononuclear cells at the periphery. Later on, the center of the lesions undergoes caseous necrosis and eventually a fibrosclerotic scar occurs.
The diagnosis is confirmed by a positive intradermal test with tuberculin, by showing acid-fast bacilli in the microscopic examination and, above all, by positive cultures in Petragnani medium. When available, polymerase chain reaction can identify even small contents of mycobacterial DNA and confirm the diagnosis in a few days.
Lupus vulgaris is another form of post-primary tuberculosis, arising in subjects with hypersensitivity towards mycobacterium tuberculosis. Today, it is rare especially in childhood.
The lesions usually start on the face, especially around the nose. The skin lesions are characterized by erythematous plaques with small, soft, micronodules, which can be easily depressed. On diascopy, the plaque acquires a characteristic yellowish color. The plaques can get ulcerated and give raise to wasting scars.
The clinical diagnosis is confirmed by a strongly positive intradermal test and in some cases by the pathological findings. Rarely the cultures grow mycobacteria.
Primary skin tuberculosis is a more rare form of cutaneous tuberculosis but characteristic of childhood. It is due to cutaneous inoculation of M. tuberculosis in a subject, who had not contact with this agent.
We are dealing with a nodular and ulcerative lesion mainly affecting the skin of the face (Fig. 729), with frequent satellite adenopathy.

Fig. 729: Primary cutaneous tubercu- losis in a 1-year-old boy.

The lesion slowly regresses in many months and can develop into a form of post-primary tuberculosis. On light microscopy, an acute infiltrate of polymorphonuclear leukocytes can be initially observed. With time, the infiltrate acquires the characteristics of the tubercular granuloma with disappearance of the bacilli. As other forms of tuberculosis, primary tuberculosis of the skin can be associated to erythema nodosum. The appearance, although exceptional, of erythema nodosum in a child should always raise the suspicion of tuberculosis. The treatment is based on the use of isoniazid (15 mg/kg per day, max 300 mg), rifampicin (10 mg/kg per day) and pyrazinamide (30 mg/kg per day) for the first 2 months, then isoniazid and rifampicin twice a week for the following 4 months.

Syphilis. Granulomatous syphilitic lesions can be observed in the primary and tertiary phase. In the child the tertiary form does not practically exist and the primary form exists only as a consequence of sexual abuse in the peripuberal period.
We are briefly mentioning congenital syphilis, which is the most frequent form in childhood, although its prevalence significantly changes with time and in various countries. For instance, in 1996, 56 cases of congenital syphilis were recorded in New York, whereas three years later the cases were more than 1,000.
A pregnant woman with recent syphilis infects the fetus through the placenta, starting from the fourth month of fetal life. When the mother is affected by latent syphilis, the probability of infecting the fetus significantly decreases. Besides the cases of negligence, the infection can be due to serological negativity. The latter can be due to a late contagion or to excessive amounts of antibodies, as in secondary syphilis.
The infection of the fetus is often massive. This is why an abortion can occur. Fetal congenital syphilis is characterized by late -after the fourth month- and repeated abortions and by hydramnios. Natimortality and perinatal mortality are also expression of a massive infection of the fetus. When the infection is less massive, because for instance the contagion occurred late, prematurity or late appearance, even after years, of the clinical signs can occur.
Therefore, a precocious congenital syphilis corresponding to the secondary period of the acquired syphilis and a late congenital syphilis corresponding to the tertiary period, are usually described.

Precocious congenital syphilis. Due to the generalized infection, whatever organ can be affected, starting from the placenta, which is usually hypertrophic. The skin is affected by a papular coppery red rash. The lesions are usually annular (Fig. 735, 736) and can involve the perianal -perianal condylomata lata- (Fig. 735) or palmar and plantar region. The latter localization is characterized by a bullous appearance (pemphigus syphiliticus). When the blisters break, the papular, infiltrated and annular lesions appear (Fig. 736). The lesions contain a lot of spirochetes, which can be shown on dark field microscopy. The lesions of the nasal mucosa (luetic coryza) are characterized by sero-hematic exudation.

Fig. 735: Perianal papular lesions (condylomata lata)

Osteochondritis of the long bones is another characteristic sign. The transition area between the cartilage and the bone appears broad and irregular. From a clinical point of view, there is a painful tumefaction, which can lead to the so-called Parrot’s pseudoparalysis (Fig. 733). Anemia, enlargement of the liver and spleen, nephrosis, interstitial pneumonia, hydrocephalus, neurological, ocular and whatever organ manifestations can also occur.

Fig. 733: Congenital syphilis: Parrot pseudoparalysis with papular lesions.

A falsely negative serology in the newborn (for instance excess of 7S IgG of maternal origin in the FTA-IgM test) can delay the diagnosis and treatment.
More frequent is the problem of the falsely positive luetic reactions, which are due to the passage through the placenta of maternal 7S IgG antibodies. The differential diagnosis of this condition is extremely important. Treating all the newborns with positive VDRL would be simple. However, from a psychological point of view, in this case the mother could feel unfairly responsible of the infection of her child. On the other hand, physicians should not ignore that at birth, although rarely, the clinical features of congenital syphilis may lack and appear later, even after many years. It is important to remember that the titer of passively transmitted antibodies rapidly decreases in the newborn till annulling themselves within the third month.
When quantitatively testing in the same session of the same laboratory the serum of the mother and that one of her child, the antibody titer of the child, in case of transmitted positivity, is never higher than that one of the mother and significantly decreases after 1 month.
More specific tests such as FTA/IgM are not available in all the laboratories and are not free from false positive and false negative results. Increased IgM in the newborn and aspecific inflammation indexes can confirm the suspicion of congenital syphilis.
A very important criterion derives from the mother history. When the mother was opportunely treated, the newborn is unlikely affected by congenital syphilis. In conclusion, treating a newborn with transmitted positivity is not right, unless in particular environment conditions the newborn cannot be opportunely monitored.
Leprosy. Leprosy is a granulomatous infectious disease due to Mycobacterium leprae. The latter can be shown in the affected tissue (Fig. 739). Skin and nerves are mainly affected. The contagion occurs following prolonged contact in predisposed subjects. This is why children are more often affected than the partner. The source of the disease is usually a relative with a not yet diagnosed lepromatous form of the disease and with a nasal secretion rich in bacilli. The contagion usually occurs in childhood.
The clinical features of the disease are due to the immunological reactivity and peripheral nerve damage. Tuberculoid and lepromatous lepra are the two ends of the clinical spectrum of the disease.
In lepromatous leprosy the specific cell-mediated immunity against the mycobacterium is depressed, leading to a significant multiplication and diffusion of bacilli in the tissues, whereas the lack of activated lymphocytes leads to a less evident neurological compromission.
On the other hand, in tuberculoid leprosy the cell mediated reactivity is evident, leading to localize the disease in a few sites and to a significant neurological compromission due to the lymphocyte infiltrate. The neurological compromission is evident both in the skin and in the peripheral nerves.
In the skin the compromission of the sensory and autonomic nerves is responsible for the loss of sensitivity and sweating in the affected areas. The more superficial, peripheral nerve trunks and those ones running in fibrous-osseous tunnels are more easily compressed by the lympho-cyte infiltrate.
As a consequence of the compression, anesthesia, muscle weakness and contractures appear. Anesthesia is in turn responsible for burns, tissue necrosis and ulcers. Leprosy reaction and erythema nodosum are a consequence of the altered immunological reactivity. Erythema nodosum is due to the deposition of immune complexes.
From a clinical point of view, the first sign is usually an area of insensitivity of the skin. The latter can be shown level with a hypopigmented area or it can be suspected and then shown level with burns or traumatic ulcers, which cannot be explained unless a defect of sensitivity is demonstrated.
As above mentioned, the two polar forms of leprosy are tuberculoid and lepromatous lepra. Borderline leprosy has intermediate characteristics.
In tuberculoid leprosy the lesions are few and characterized by an erythematous plaque with hypopigmented, insensible center. In the subject with dark skin erythema may lack. At the periphery of the plaque a thickened nerve can be sometimes palpated. The nerve can be only affected without involvement of the skin.

Fig. 738: Lepromatous lepra in a 6-year- old boy.

Lepromatous leprosy. It is characterized by mucous signs, essentially exudating and hemorrhagic rhinitis, and cutaneous signs such as erythematous and hypopigmented macules, papules, nodules (Fig. 738) and diffuse infiltration of the skin. In this form lepromatous reactions are frequent. The latter are characterized by general vasculitis, and symptoms, which are probably due to immune complex vasculitis, and cutaneous nodules, mainly of the face and extensor aspect of the arms, which can suppurate and ulcerate.

The nervous involvement in leprosy mainly affects the sensory function. In the severe forms the autonomic nervous system is consistently affected. Rarely, the motor component is exclusively affected.
Ocular lesions till blindness are not exceptional in leprosy.
The diagnosis of leprosy is clinical, thanks to the presence of anesthesia, nerve thickening and typical cutaneous lesions, and biological by showing Hansen bacilli in the smears from the nose and cutaneous lesions.
The treatment of leprosy is essentially based on rifampicin, dapsone and clofazimine. The paucibacillary patients are treated with two associated drugs (rifampicin and dapsone) for six months. Multibacillary patients are treated with three associated drugs (rifampicin, dapsone and clofazimine) for two years. After withdrawing treatment, paucibacillary patients are monitored for two years, whereas multibacillary patients for five years.
The treatment of the leprosy reactions is based on the use of corticosteroids and in the mild cases of thalidomide.

Granulomatous mycoses

We are treating in this chapter granulomatous candidiasis, kerion and sporotrichosis.

Granulomatous candidiasis. It is one of the most severe forms of chronic mucocutaneous candidiasis. Unlike the other three forms, which are transmitted by an autosmoal dominant or recessive trait, this form probably is not inherited. It is particularly severe, because characterized by esophageal involvement, other infections and bronchiectasias. From a dermatological point of view, granulomatous candidiasis is characterized by hyperkeratotic and nodular lesions, which are mainly located on the scalp. Granulomata are probably due to the accumulation of polymorphonuclear leukocytes, which are not able to destroy candida elements. The cutaneous lesions are very widespread and the nail compromission is marked (Fig. 740, 741). The prognosis of granulomatous candidiasis, as well that one of the other forms of chronic muco-cutaneous candidiasis changed with ketoconazole and other systemic anti-mycotic drugs. The milder forms sometimes regress after only one cycle of these drugs and the regression is sometimes definitive. More often more cycles of the drugs should be administered.

Fig. 740: Granulomatous candidiasis. Perionyxis with severe nail involve- ment (onychogryphosis). There are also granulo- matous lesions on the face and scalp.

Kerion. Kerion is usually described as an inflammatory ringworm, whereas the term non inflammatory ringworm is reserved to tonsurating ringworms. Really, inflammation is also present in tonsurating ringworm, as shown by its scaling. Kerion is characterized by a severe granulomatous inflammation, which is followed by suppuration of the lesions. The inflammation is so marked that leads to the regression of the mycotic lesions, even without a specific treatment. As a matter of fact, kerion was the only ringworm regressing before puberty when griseofulvin had not yet appeared. In that time tonsurating worms went on till puberty, if children were not treated with aggressive therapy, such as thallium acetate or roentgen depilation, which were associated with severe side effects, till death.

Fig. 745: Inflammatory ring- worm (kerion) localized on the right parietal and nuchal region.

Kerion (Fig. 745) is caused by the same agents, which are responsible for tonsurating ringworm, therefore today by microsporon canis in most cases. The different clinical feature is therefore due to the individual reaction of the subject. From a clinical point of view, the lesions appear intensely erythematous and infiltrated, eventually giving raise to a granulomatous plaque, which is clearly defined and raised for 1-2 cm. The suppurative process follows, leading to discharge of pus, spontaneously and at palpation. Often, regional adenopathy coexists and superimposed bacterial infections are frequent. Constitutional symptoms and intense, spontaneous and at palpation, pain are present. After a couple of months, even without a specific antimycotic treatment, the lesions tend to spontaneously regress. The hairs lack almost completely in the inflammatory areas.

After the regression of the inflammatory lesions, the hairs only partially regrow and remain more sparse in the affected areas.
The diagnosis by fresh mycological examination is more difficult than in tonsurating ringworms, due to the lack of broken hairs and the presence of pus.
The treatment of choice is griseofulvin at a dose of 15 mg/kg per day for 30 days. If the syrup is not available, the pills can be pulverized with a spoonful and administered after the meals. At least initially, a systemic antibiotic treatment is often associated to the antimycotic drugs. It is also useful an antiinflammatory local treatment with wet compresses soaked in weak disinfectants at environment temperature.
According the Italian law, infected children can attend the school provided they wear a hat. However, it is better to avoid the suspicious looks of friends and above all of adults, with their fear of contagion. Children could again attend the school when acceptable from an esthetic point of view.

Fig. 742: Lymphatic sporo- trichosis.

Sporotrichosis. Sporothrichosis is a mycotic infection with a particular tropism for the lymph structures. It is caused by Sporotrichum schenckii. The disease is characterized by a particular geographical distribution, preferring the temperate and tropical areas. The fungus penetrates into the skin usually of the lower limbs through often traumatic breaks. Sporotrichosis is more frequent in male adults, who are professionally exposed such as farmers and miners. However, it can also affect children (Fig. 742, 743), especially when they walk barefoot on the ground. Once entered the skin, the fungus causes a dermal and subcutaneous granulomatous reaction, with tendency to the colliquation necrosis. According to the individual reaction, the fungus can remain in the site of penetration, be transmitted along the lymphatic structures till the regional lymph nodes or rarely give raise to a systemic disease.

The lymphatic form is more frequent, starting with a nodular lesion, which is usually localized on a leg or foot. The initial lesion, when is not diagnosed and precociously treated, undergoes colliquation necrosis and ulceration. Later on, the involvement of the lymphatic vessels is betrayed by the hardening of the draining lymphatic vessels and then by the appearance on the same vessels of other granulomatous lesions, which then tend to be colliquated and ulcerated. When the disease is not treated, the lymph nodes can be affected and then ulcerated, whereas the previous lesions can spontaneously regress.
In the more rare localized form, the disease, probably due to a high degree of immunological resistance of the patient, remains localized in the site of primary inoculation, running the same stages already described in the lymphatic form, till the possible spontaneous regression.
On the other hand, the systemic form, which is probably due to anergy of the patient, for instance alcoholic, is characterized by disseminated lesions of the lungs, joints, meninges and skin.
Cutaneous sporotrichosis should be mainly differentiated by mycobacteriosis and leishmaniasis. The history (profession and origin of the patient), the smear from the lesions (leishmaniasis) and the culture (mycobacteriosis) make usually easy the differential diagnosis. Cultures on Sabouraud medium grow whitish, wet and superficially rough colonies, which progressively turn to brownish, chocolate-like color.
The treatment is based on the use of potassium iodide in saturated solution (potassium iodide 10 g, distilled water 10 ml). Initially, 3-5 drops of the solution, 3 times a day, far away from the meals, are given. The dose is then daily increased till to 30-50 drops 3 times a day. The treatment should be continued for 20-30 days, till the healing of the lesions.
Instead of potassium iodide, itrakonazole, at a dosage of 100-200 mg per day in adults (3 mg/kg per day in children) can be given for the same period of time.

Granulomatous infestations

Among the agents responsible of granulomatous reactions of the skin, we are treating leishmaniasis, scabies and tick bite.
Leishmaniasis. The disease is caused by flagellate protozoa of the genus Leishmania, which undergo a development cycle in the intestine of insects of the genus Phlebotomus in Europe.
In the vertebrate host the amastigote (lacking the flagellum) form is found into the cells of the reticulo-endothelial system as round, 2-3m in diameter bodies, which characteristically present two eccentric, basophilic nuclei (the smaller is kinetoplast).
The infection is usually transmitted through the sting of the Phlebotomus. Vertebrates are the habitual host and the reservoir of the infestation. Their life habits and the biological cycle of the Phlebotomus influence the distribution of the disease in particular geographical areas.
Humans, which are usually accidental hosts, can present lesions on the skin or in internal organs. Both the localizations are usually due to the same parasite. However, cutaneous and visceral leishmaniasis are unlikely shown in the same subject.
Cutaneous leishmaniasis is characterized by a nodular granulomatous lesion, which affects exposed areas, more frequently in children (Fig. 746).

				The nodule is firm and elastic with a characteristic central area of softening, due to a necrotic process. The softening area is usually appreciated when a scrap of tissue is removed with the spoonful to show the parasite. The central area tends to get ulcerated and covered by a crust. After many months the lesion tends to regress with fibrosis. This is why leishmaniasis is called "one year button". The lesion can be larger and form a plaque (Fig. 747) or less infiltrated (Fig. 748) and yellow-orange (lupoid leishmaniasis).
Fig. 746: Nodular leishmaniasis.		Fig. 748: Tuberculoid leishmaniasis.

The diagnosis is usually clinically suspected taking into account the clinical features and the origin of the patient.
The clinical diagnosis is usually confirmed by showing the parasite within the lesions. A scrap of tissue is removed from the lesion, smeared on a slide, fixed with methanol and finally colored with Giemsa. In the granulomatous form parasites are usually shown rather easily, inside the histiocytes (Fig. 750) or free in the interstitial tissue.

In the paucibacillary forms a delayed cutaneous reaction can be searched for after an intradermal injection of leishmanin (Fig. 749), namely an extract of leishmania in phenol saline. When interpreting this reaction, physicians should take into account that in endemic areas after childhood there are many sensitized subjects. Leishmanias can also be grown from a scrap of tissue inseminated in brain-heart medium with red cells of rabbit (Fig. 751). Although the cutaneous lesions spontaneously heal, the time, which is necessary for healing, cannot be predicted. This is why cutaneous leishmaniasis is usually treated with intralesional injection of antimony salts.

Fig. 750: Typical binuclear appearance of intraphagocytic Leishmania in the smear from a skin lesion.

Fig. 751: Flagellate form of Leishmania in culture (Brain-heart with defibrinated blood of rabbit)

When the nodule is small a single intralesional injection is enough, whereas larger lesions require more than one injection in order to infiltrate all the lesions. Antimony salts at a dose of 20 mg/kg per day per intramuscular injection are not devoid of side effects. This is why the systemic treatment should be reserved to disseminated forms, which are at risk for unaesthetic scars, and continued till the healing of the lesions (usually 10-15 days).
Scabies. Scabies is an infestation due to a mite, namely Sarcoptes scabiei. The variety hominis is reponsible for human scabies and specific of the human skin, namely it is able to reproduce itself only in the human epidermis. There is a specific mite for every mammalian, namely the mite of dog scabies, that one of the cat scabies etc., which are able to reproduce themselves only in the epidermis of the dog, cat etc.. These mites can sting the human. However, they cannot reproduce themselves and thus persist in the human epidermis. Therefore, once treated the cat or dog, the lesions caused in the man by their specific mites spontaneously regress.
The female mite, after mating, excavates a burrow inside the horny layer and here deposits her eggs. The latter within a few days hatch and the emerging larvae get adult and mate them selves, giving raise to a new cycle. The infestation regresses only when all the adults and larvae are killed.
The mite of scabies survives for a very short time out of the human skin. This is why the contagion is interpersonal, following a close contact, usually sleeping in the same bed. The contagion also depends on the predisposition to be affected and the amount of mites.
The predisposition does not depend on specific immunity, which does not exist, probably because the mites stay very superficially and do not come in contact with the immunocompetent structures of the skin. On the other hand, the predisposition is natural and different in the various subjects. This partially explains the strange resistance of some subjects of the same family group.
The amount of mites is also important, as shown by the so-called Norwegian scabies, which is highly contagious because the skin is plenty of burrows and then is teeming with mites. The amount of mites is also important in determining the incubation period of the disease, ranging between a few days and several weeks. From an epidemiological point of view, sex and age of the subject are not important. With regard to the age, scabies may occurs from the second week of life till death.
The itching is the most important symptom, which often leads the patient to the doctor. The most important characteristic of the scabies itching is that it is often simultaneously present in many members of the family group and that it arises in the various subjects of the same family group with an interval of 2-3 weeks. In spite of this rule, it is possible that only a subject remains affected in a family group for a long time. This usually occurs in the subjects, who have and use all the hygienic comforts.
We usually read that scabies itching prevails during the night and deteriorates when going to bed. Really this is the rule in all the most itching disorders and particularly in atopic dermatitis.
The lesions of scabies have a characteristic morphology and distribution. The initial and more characteristic lesion is the burrow (Fig. 756), namely a linear lesion, which is 4-12 mm long and less than 1 mm large. The latter is due to the walking of the female mite inside the horny layer with deposition of the eggs. On the other hand, the pearly vesicle, which can be isolated or at the end of a burrow, is found much more rarely. The vesicle probably corresponds to the end of walking of the female and can be more easily observed in the palmar region, where it can persist longer thanks to the thicker horny layer. The pearly vesicle should be differentiated from the palmar and plantar pustules, which can be shown after a treated scabies in the first year of life. The latter are turbid and do not contain mites.
Besides burrows and pearly vesicles, which can be considered the specific lesions of scabies, there are other lesions in this disorders, such as papules and vesicles of various size and scratch marks of various type.
Moreover, there are granulomas. The latter are 5-20 mm in size, reddish or red-brownish, firm nodules. These nodules, which are characteristic of children, often arise some weeks after the onset of the disease and do not contain mites. These nodules should probably be considered as a foreign body reaction against exogenous material, which penetrated inside the dermis by scratching. Characteristically, the nodules periodically get more inflamed, with transitory significant increase of itching and size.
Finally, there are eczematous and impetiginized lesions, which are expression of the complications due to scratching.
The presence of burrows, pearly vesicles, nodules, eczematous and impetiginized lesions gives a characteristic polymorphism to the clinical features of scabies.
Besides this polymorphism, the distribution of the lesions immediately suggests the diagnosis of scabies. The distribution of the lesions is so characteristic that it should be mentioned in details as follows: interdigital spaces of the hand, ulnar margin of the hand, flexor aspect of the forearm, extensor aspect of the elbow, anterior pillar of the armpit, genitalia, subgluteal furrow and plantar surface in children. The head is never affected, except for the first months of life. Primary and secondary genitalia are even more often affected in adolescents and adults. Physicians should also remember that the ulnar aspect of the hand, which is rarely involved in other skin disorders, has a high diagnostic value. We do not know exactly the reason of a so typical distribution, although somebody hypothesized that are elective the sites that cannot be easily scratched.
Scabies should be differentiated from all the other itchy skin disorders and particularly atopic dermatitis (AD). The family history for itching can be positive in AD. However, it is unlikely that two subjects of the same group started to scratch with an interval of a few weeks each other. The elective sites of AD are different, its lesions are less polymorphous and there are not gross nodules. When burrows are identified, the differential diagnosis is easier. In the doubtful cases the research of parasites in the lesions can be diriment.
The treatment is based on some basic principles, which should be known and respected. They are more important than the choice of the acaricide. Scabies does not give immunity and then can relapse more times. This is why all the subjects with suspected scabies belonging to the same family group must be simultaneously treated. The acaricide treatment must be repeated 5-7 days after the first rubbing, to be sure of killing the mites deriving from the eggs hatched after the first treatment. The treatment should be performed on the entire skin surface, except for the head, after a warm bath aimed at soaking the more superficial layers of the skin and therefore expose the parasites to the direct action of the acaricide. The treatment itself is irritant and can cause itching.
Practically, after a warm bath, the acaricide is rubbed with a gauze on the entire skin surface, insisting on the elective areas and the areas more affected by the lesions. The rubbing should be repeated 2-4 times with an interval of 12-36 hours. Under 1 year of age it is better an interval between rubs larger than 24 hours. As acaricide, 25% (15-20% under 1 year) benzyl benzoate in petrolatum oil can be used (shake well before using) or one of the other drugs actually on sale. We are waiting for ivermectin, which is not yet on sale for human usage.
After treatment, nodules can persist for a long time, even many months. Periodically, nodules undergo crises of itching and inflammation. In this case topical corticosteroids creams should be given. A specific treatment is not necessary, unless numerous new lesions appear on the entire skin surface.
Besides nodules, also palmar and plantar pustules can persist for a long period of time in children aged less than one year. Also these pustules do not contain mites and do not need a specific treatment for scabies.

E. Bonifazi