E. Ruocco

Pyoderma gangrenosum: an updated review

Pyoderma gangrenosum is a rare, ulcerative, cutaneous condition. First described in 1930, the pathogenesis of pyoderma gangrenosum remains unknown, but it is probably related to a hyperergic reaction. There are various clinical and histological variants of this disorder. Pyoderma gangrenosum often occurs in association with a systemic disease such as inflammatory bowel disease, rheumatologic disease, paraproteinaemia, or haematological malignancy. The diagnosis, mainly based on the clinical presentation and course, is confirmed through a process of elimination of other causes of cutaneous ulcers. Local treatment may be sufficient for mild disease, while for severe cases, systemic immunosuppressants are the mainstay. Long‐term treatment with these agents is often required, but this can expose patients to adverse side‐effects.

Helicobacter pylori infection but not small intestinal bacterial overgrowth may play a pathogenic role in rosacea

Background and aims Recent studies suggest a potential relationship between rosacea and Helicobacter pylori (H. pylori) infection or small intestinal bacterial overgrowth (SIBO), but there is no firm evidence of an association between rosacea and H. pylori infection or SIBO. We performed a prospective study to assess the prevalence of H. pylori infection and/or SIBO in patients with rosacea and evaluated the effect of H. pylori or SIBO eradication on rosacea. Methods We enrolled 90 patients with rosacea from January 2012 to January 2013 and a control group consisting of 90 patients referred to us because of mapping of nevi during the same period. We used the 13C Urea Breath Test and H. pylori stool antigen (HpSA) test to assess H. pylori infection and the glucose breath test to assess SIBO. Patients infected by H. pylori were treated with clarithromycin-containing sequential therapy. Patients positive for SIBO were treated with rifaximin. Results We found that 44/90 (48.9%) patients with rosacea and 24/90 (26.7%) control subjects were infected with H. pylori (pu2009=u20090.003). Moreover, 9/90 (10%) patients with rosacea and 7/90 (7.8%) subjects in the control group had SIBO (pu2009=u20090.6). Within 10 weeks from the end of antibiotic therapy, the skin lesions of rosacea disappeared or decreased markedly in 35/36 (97.2%) patients after eradication of H. pylori and in 3/8 (37.5%) patients who did not eradicate the infection (pu2009<u20090.0001). Rosacea skin lesions decreased markedly in 6/7 (85.7%) after eradication of SIBO whereas of the two patients who did not eradicate SIBO, one (50%) showed an improvement in rosacea (pu2009=u20090.284). Conclusions Prevalence of H. pylori infection was significantly higher in patients with rosacea than control group, whereas SIBO prevalence was comparable between the two groups. Eradication of H. pylori infection led to a significant improvement of skin symptoms in rosacea patients.

Granuloma annulare in a site of healed herpes zoster: Wolf's isotopic response.

A case of granuloma annulare that developed in a site of healed herpes zoster is reported. Polymerase chain reaction failed to detect VZV DNA in a biopsy specimen. The occurrence of different types of cutaneous reactions in a body area previously affected by herpes virus infection is known as Wolfs isotopic response. Pathogenesis may be due to a local neuroimmune dysregulation set off by herpesvirus‐induced lesions of dermal sensory nerve fibres.

Coexistence of malignancy (skin cancer) and immune disorder (discoid lupus erythematosus) on a burn scar: a concrete example of ‘immunocompromised district’

Features of psychopathological disorders could not be found. Nevertheless, when approached on the subject of suspicions concerning the origin of the haematomas, the children kept silent. However, the three siblings on request independently answered a question for psychic stress in the past, that their beloved cat had died 1 week before appearance of the haematomas. Blood tests and immunology were unremarkable, and serology for toxocariasis was negative. Analysis of blood clotting revealed an extended collagen–epinephrine bleeding time in all three children without any increase in the collagen–ADP bleeding time; plasma clotting parameters were within the normal reference range. There was no evidence that the children had taken nonsteroidal anti-inflammatory drugs or other drugs that could affect the test results. A typical autosensitivity test was undertaken with autologous and washed erythrocytes and showed a positive result only in the 12-year-old girl. Based on the dermatological examination, Gardner–Diamond syndrome (GDS) was considered. The syndrome was named after Frank H. Gardner und Louis K. Diamond, who in 1955 were the first who systematically reported cases of painful bruising. Women are predominantly affected; only a few cases describe affected men. Furthermore, GDS is associated with symptoms such as abdominal pain, nausea, vomiting, diarrhoea and headache. Prodromal symptoms such as pain, heat, burning, itching and pulsating are described before the intradermal bruising appears, which correlates with the symptoms reported by the children. The pathogenesis is still uncertain; a role of erythrocyte antibodies was suspected by Gardner and Diamond. Latest publications define GDS as an autoimmune vasculopathy with sensitization to phosphatidylserine, a component of the erythrocyte stroma. It is assumed that tissue-bound erythrocytic antibodies lead to the development of immune complexes and complement activation. In several publications, a psychogenic component has been discussed as an inducing factor. No curative therapy has been established, but it is considered that medications influencing the capillary tonus, the permeability of vessels and the rheological properties of blood might be advisable. Some authors assert a positive effect of psychiatric therapy, particularly in younger patients. The three siblings were discharged from the hospital after 6 days of inpatient stay when the results of the additional examination arrived. Although GDS is a rare disease, a case in which three siblings develop co-occurring symptoms is extraordinary, especially as very few male cases are known. This could constitute an argument against internal causes (in the case that it is not infectious). Because of the patterned arrangement of the haematomas, an interaction of an exogenous and endogenous component, possibly self-adduction through some trigger, must be assumed, but cannot be proved. As the main diagnostic criterion (skin test) was negative in the two younger siblings, GDS could not be proved but was strongly suspected. Results of interdisciplinary cooperation revealed clearly that there was no evidence for maltreatment, and any allegation of child abuse was lifted from the parents.

Opportunistic metastatic porocarcinoma after saphenous venectomy for coronary bypass surgery

Immunocompromised areas of the skin, caused by chronic lymphoedema, paraplegia, infections or traumas, represent a site of regional neuroimmunocutaneous destabilization, termed the immunocompromised cutaneous district (ICD), in which malignancies and other opportunistic disorders are more likely to occur. We report the case of a metastatic porocarcinoma (PC) occurring on a lymphoedematous limb in a 72‐year‐old man. We reviewed the literature to better understand the potential pathogenetic mechanisms behind this condition. It has been reported that removal of the leg vein destroys the medial group of the superficial lymphatic vessels and alters the normal lymph drainage of the leg, predisposing to recurrent cellulitis. Our observations suggest that saphenous venectomy can induce development of an ICD. We suggest that PC, a rare cutaneous tumour, should be included in the growing list of tumours arising in the ICD.

A possible relationship between metal implant-induced intralymphatic histiocytosis and the concept of the immunocompromised district

immunocompromised district Editor, We read with great interest and enthusiasm the case report by de Unamuno Bustos et al., published in the May issue of the International Journal of Dermatology. The Spanish authors described the case of a 74-year-old woman who developed an intralymphatic histiocytosis (IH) of the right upper limb two months after the placement of an orthopedic metal implant for a humerus fracture. In the course of discussing the pathogenesis of this rare skin disorder, the authors refer to the different pathogenic proposals advanced before their observation. In particular, they stress that the pathogenesis of IH has still not been defined and that some authors speculate that IH may be an early stage of reactive angioendotheliomatosis, whereas others think it may result from the lymphatic drainage of histiocytes from the joints, particularly in subjects affected by rheumatoid arthritis. However, this intriguing paper makes no reference to the possible pathogenic role of metal implants in such variants of IH. We think that metal implant-associated IH may be considered the umpteenth unquestionable instance of the immunocompromised district (ICD). The ICD is a quite recently introduced pathogenic concept, which gathers under its definition the whole group of opportunistic disorders (tumors, infections, and immune disorders) that develop at cutaneous sites that are immune-marked by previous clinical events, including lymphedema, herpetic infection, vaccination, burn, trauma, and neurological injury. In the case described by de Unamuno Bustos et al., orthopedic surgery for placement of the metal implant would inevitably damage the lymphatic network, thus altering normal lymph drainage. This alteration of immune cell trafficking provokes an immune destabilization of the area served by interrupted or injured lymphatic vessels, making it prone to the development of opportunistic disorders, such as IH in this case. Inter alia, in support of our hypothesis, Requena et al. have already expressed the same concept: in a discussion of the pathogenesis of IH, they postulated that lesions might result from lymphangiectasia or lymphatic obstruction because of congenital or acquired damage (such as that caused by infection, surgery, trauma, or radiation), without referring to the concept of the ICD. Metal implant-associated IH further enriches the wide spectrum of the pathogenic concept of the ICD, which seems, in our opinion, to represent the best and most convincing way to explain the occurrence of localized opportunistic skin disorders strictly confined to the immuneconditioned cutaneous area. It is worth noting the increasing number of case reports that have appeared in the dermatological literature describing instances in which either a hindrance to lymph circulation or damage to sensory nerve fibers has paved the way for the onset of an opportunistic skin disorder. This validates the novel unifying concept of the ICD, even if the complex mechanisms at the basis of this phenomenon remain to be clarified and require further investigation.

Cutaneous leishmaniasis treated with itraconazole.

Leishmaniasis is a human disease produced by a parasite of the Leishmania genus transmitted by prick of an infected female sandfly. The disease occurs clinically with either cutaneous, mucocutaneous or visceral form, depending on the infective species and the immune status of the patient. Antimonial drugs are the current treatment of choice for all clinical forms. We report a case of cutaneous Leishmaniasis in a young girl successfully treated with itraconazole.

Tinea capitis mimicking tufted hair folliculitis.

We report a case of tinea capitis mimicking tufted hair folliculitis in a 56‐year‐old European man, who presented with a 4‐year history of pain and erythema in an area of scarring alopecia of the occipital scalp, with scales and tufts of hair emerging from individual follicles. Histological examination showed hair plugging, and a dense perifollicular infiltrate of plasma cells, lymphocytes, and neutrophils. There was widespread scarring and fibrosis. Bacterial cultures were negative for Staphylococcus aureus, but fungal cultures and periodic‐acid–Schiff stain were positive for Trichophyton tonsurans. Videodermatoscopy of the lesion showed a pattern consistent with folliculitis decalvans. Diagnosis was made on the basis of the clinical, histological, microbiological and videodermatoscopy data. After 30u2003days of systemic antifungal treatment, there were a substantial clinical improvement and disappearance of pain. After 5u2003months, a residual cicatricial area was seen with some hair tufts emerging from a single orifice.

Ulcerative colitis associated with leukocytoclastic vasculitis of the skin.

Ulcerative colitis may be associated with a number of skin lesions such as erythema nodosum and pyoderma gangrenosum. We here describe an unusual case of a 33-year-old-caucasian male with ulcerative colitis and skin lesions diagnosed as leukocytoclastic vasculitis. An initial treatment with oral deflazacort led to little benefit, while treatment with oral mesalazine caused remission of the skin and intestinal manifestations in 2 weeks.

The correct meaning of the term ‘immunocompromised’: a necessary explanation

Editor We appreciated Simon et al.’s reply to our letter to the Editor concerning acne and local immunity and completely agree with them that in the patient they reported there was hyperactivation (and not suppression) of immunity. Based on the activation of local immunity, Simon et al. have expressed their belief that their clinical case could not fall within the novel concept of immunocompromised district. All the same, in our opinion, the case remains an instance of immunocompromised district because the term ‘immunocompromised’ generically indicates an alteration of the immune response, and not necessarily reduction of it. In fact, this alteration, depending on the neurotransmitters and immune cells each time involved, can be either defective or excessive, as precisely it occurred in Simon et al.’s patient. We thought we have made it clear in our previously published articles, in particular in the lowest box of Fig. 4, that the immunocompromised district can be identified as a peculiar site of regional destabilization of the neuroimmunocutaneous system (an intriguing subject extensively dealt with by Misery) where many and various disorders can take place and remain confined. Among these disorders, some clearly indicate local reduction of immunity (e.g. opportunistic infections and tumours), some point to a locally exaggerated activation of immunity (e.g. bullous pemphigoid, pemphigus, lichen planus, discoid lupus erythematosus, drug eruptions and acne). This is the reason why we have always talked of immunocompromised (and not immunosuppressed) district in our articles and oral presentations on the topic.