Pustular skin disorders: diagnosis and treatment

The differential diagnosis for pustular skin disorders is extensive. The distribution of the lesions and the age of the patient are characteristics that may provide strong clues to the etiology of cutaneous pustular eruptions. In adults, generalized pustular dermatoses include pustular psoriasis, Reiter's disease and subcorneal pustular dermatosis. Medications can cause generalized pustular eruptions, such as in the case of acute generalized exanthematous pustulosis; or more localized reactions, such as acneiform drug eruptions, which usually involve the face, chest and back. Localized pustular eruptions are seen on the hands and feet in adults with pustulosis palmaris et plantaris and acrodermatitis continua (both of which may be variants of psoriasis); on the face in patients with acne vulgaris, rosacea, and perioral dermatitis; and on the trunk and/or extremities in patients with folliculitis. A separate condition known as eosinophilic folliculitis occurs in individuals with advanced human immunodeficiency disease. Severely pruritic, sterile, eosinophilic pustules are found on the chest, proximal extremities, head and neck. Elevated serum immunoglobulin E and eosinophilia are often concurrently found. In neonates, it is especially important to make the correct diagnosis with respect to pustular skin disorders, since pustules can be a manifestation of sepsis or other serious infectious diseases. Generalized pustular eruptions in neonates include erythema toxicum neonatorum and transient neonatal pustular melanosis, both of which are non-infectious. Pustules are seen in infants with congenital cutaneous candidiasis, which may or may not involve disseminated disease. Ofuji's syndrome is an uncommon generalized pustular dermatosis of infancy with associated eosinophilia. As in adults, neonates and infants may develop acne or scabies infestations. In this article, we review the most common pustular dermatoses and offer a systematic approach to making a diagnosis. We also report the most up-to-date information on the treatment of these various cutaneous pustular conditions.     

Sterile eosinophilic pustulosis

Sterile eosinophilic pustulosis (SEP) first described by Ofuji et al. in 1970 as "eosinophilic pustular folliculitis," is obviously a new entity. The majority of patients are Japanese. So far only four European cases have been reported. However, we have recently observed a 46-year-old Greek male (the fifth case in Europe) with the typical clinical features of SEP: repeated eruptions of aggregated pruritic (follicular) papulopustules (1-2 mm in diameter). The eruptions developed in slightly elevated erythematous patches localized on the extremities, face, and trunk. Histologic examination revealed intraepidermal pustules containing eosinophils and moderate dermal infiltrates with mononuclear cells and eosinophils around follicles, sebaceous glands, and vessels. In addition to the characteristic clinical and histological features, our patient showed all the typical laboratory findings previously described: negative bacterial cultures from the pustules, blood eosinophilia, increased total IgE, negative reactions to intradermal tests of recall agents. Furthermore, the rate of suppressor/cytotoxic T-cells (OKT 8-cells) in peripheral blood was significantly diminished, and mitogenic stimulation of lymphocytes in vitro was negative (decreased LTT). These laboratory data resemble the immunopathological findings in atopic diseases. On the other hand, seborrheic skin with sterile eosinophilic pustules predominantly occurring in skin areas rich in sebaceous glands seems to be another remarkable sign of SEP. The question of whether the co-incidence of atopylike immunological constellation and seborrheic skin observed in SEP has pathogenetic importance, however remains open. Apart from corticosteroids and sulfones, a favorable therapeutic effect may be obtained by inhibitors of cyclooxygenase. In our case indomethacin caused a quick and lasting therapeutical benefit.     

Acute exanthematous pustular drug eruption induced by mexiletine

A 56-year-old man developed infiltrated erythemas on the trunk, extremities, and face with marked facial edema, one month after taking mexiletine hydrochloride for his arrhythmia. A number of pustules were also noted on the surface of erythemas on his chest and face. Laboratory examination showed liver dysfunction and hypereosinophilia. The culture from pustules was sterile. Histological examination of the biopsied skin from a pustular lesion revealed a subcorneal abscess, and perivascular infiltration of lymphocytes, mononuclear cells and eosinophils in the upper dermis. The skin lesions and facial edema as well were improved within three weeks by withdrawal of mexiletine hydrochloride. Patch tests with 10% and 20% mexiletine hydrochloride in petrolatum showed positive reaction, however, pustules were not provoked on the tested site. We conclude that pustules, infiltrated erythema and facial edema were the signs of acute exanthematous pustular drug eruption induced by mexiletine hydrochloride.     

Vesiculopustular eruptions in Down syndrome neonates with myeloproliferative disorders

BACKGROUND: Infants with Down syndrome are at increased risk for hematologic abnormalities, including leukemoid reaction, transient myeloproliferative disorder, and congenital leukemia. The differential diagnosis of a vesiculopustular eruption in an infant with Down syndrome and these hematologic abnormalities is broad and includes benign, self-limited disorders as well as life-threatening infections. OBSERVATION: We describe 3 newborns with Down syndrome and vesiculopustular eruptions associated with myeloproliferative disorders during the neonatal period. These lesions differ from other neonatal vesicular eruptions in that they have a unique distribution, display pathergy, and contain immature hematopoietic cells similar to circulating blast cells. Resolution occurs without treatment as the hematologic disorder subsides. CONCLUSIONS: Infants with Down syndrome and hematologic abnormalities may have a cutaneous eruption that has characteristic clinical and histopathologic findings. It is possible that this eruption has been unrecognized in the past because of its self-limited course. Whether this eruption is a prognostic factor for the subsequent development of leukemia is uncertain.     

Generalized pustular drug eruptions: confirmation by in vitro tests

Background Generalized pustular eruptions are characterized by acute onset of aseptic pustules in febrile patients with leukocytosis after exposure to the offending drug. They have been regarded as uncommon manifestations of adverse drug reactions. Until now few confirmation studies have been carried out. Objective Our purpose was to describe a series of patients with generalized pustular drug eruption. The diagnosis and etiological role of drugs in these cases was confirmed by two in vitro tests, namely the macrophage migration inhibitory factor (MIF) and the mast cell degranulation (MCD) tests. Methods The clinical, pathological and laboratory findings in six patients with generalized pustular eruption were studied prospectively. The MIF and MCD tests were performed with the drugs taken by the patients. Results The dermatological manifestations included numerous pustules on large erythematous areas, papules and erythema multiforme-like lesions. The pustular eruption developed between 12 h and 5 days after the administration of the provoking drug. The histopathological changes were characterized by subcorneal pustules, papillary edema and mixed cell inflammatory infiltrate. In two biopsies the infiltrate displayed numerous eosinophils. Laboratory investigations revealed leukocytosis with neutrophilia (4 of 6 patients) and eosinophilia and hyperimmunoglobulinemia E (2 of 6 patients).MCD tests with the suspected drugs (Ampicillin, Cefazolin, Tetracycline, Griseofulvin, Enalapril Maleate) were positive in all patients. Positive MIF results were seen in five of the six patients. Withdrawal of the drug led to fast recovery. Conclusion The diagnosis of pustular drug eruptions depends on circumstantial evidence, some characteristic clinico-pathological findings and exclusion of alternative diagnoses of other disseminated pustular eruptions. In vitro tests, namely MIF and MCD tests, are a useful diagnostic aid in the identification of the offending drugs.     

Amicrobial pustular dermatosis in two patients with immunological abnormalities

We report two patients with severe amicrobial pustular dermatosis with immunological abnormalities: a 63-year-old woman with a 30-year-history of discoid lupus erythematosus and sicca syndrome, and a 35-year-old woman with high levels of gamma-globulinemia and positive antinuclear antibodies. Both patients presented with crusty and eroded erythematous plaques studded with aseptic pustules on the back, face, and scalp. Histological examination showed acanthosis, neutrophilic exocytosis to the epidermis, and neutrophilic and lymphocytic infiltration with nuclear dust in the dermis. These patients were diagnosed as having "amicrobial pustulosis associated with autoimmune diseases". The eruptions improved with combination treatment of oral prednisolone with cyclosporin A or diaminodiphenylsulphone. Although the pathogenesis remains unclear, amicrobial pustular dermatosis might be one of the cutaneous complications in autoimmune diseases.     

Parvovirus B19 infection presenting as 'bathing trunk' erythema with pustules

A 7-year-old girl presented with acute vulval erythema and pustules, associated with a petechial eruption in her flexures and over her feet. There was a mild prodromal illness and the patient was afebrile. There were minimal symptoms associated with the rash. Skin and throat swabs were negative and blood examination showed mild neutrophilia and lymphopaenia. Parvovirus B19 IgM was detected on serology and cutaneous features resolved within 4 days. This is a further case of parvovirus B19 infection presenting as a 'bathing trunk' exanthem that has unique dermatologic features, including the presence of pustules and distant petechiae.     

Tumor necrosis factor-alpha inhibitors and acne fulminans: Friend or foe?

Acne fulminans (AF) is an uncommon variant of inflammatory acne with abrupt eruption of painful nodules, pustules, and hemorrhagic ulcerations, often associated with systemic symptoms. Paradoxical adverse reactions to tumor necrosis (TNF)-alpha inhibitors have been reported, and rare cutaneous complications include pyoderma gangrenosum, Sweet syndrome-like hypersensitivity eruptions, and pustular folliculitis. We report an unusual case of AF in a patient with Crohn disease that worsened with doses of adalimumab, which is considered a second-line treatment for AF. This case highlights that acneiform eruptions may be an underreported paradoxical adverse reaction to anti-TNF alpha therapy.     

Aleukaemic leukaemia cutis presenting as a benign-appearing eruption

A 68-year-old Caucasian male presented with a 5-week history of a widespread pruritic papular eruption. Histology from a papule on the left shoulder showed a dense dermal infiltrate of large mononuclear cells which were positive for leucocyte common antigen, KP1 and PGM1, with an MIB-1 proliferating fraction of 40%, diagnostic of acute monocytic (M5) leukaemia cutis. Full blood count revealed pancytopaenia but no blasts. Bone marrow aspirate showed reduced red cell precursors and 10% blasts, consistent with myelodysplastic syndrome (refractory anaemia with excess blasts). The patient was managed with a 3 unit transfusion of packed red cells, after which his skin eruption resolved within 6 weeks and his peripheral blood counts returned to normal. No chemotherapy was administered. In conclusion, leukaemia can present in the skin, the eruption may be nonspecific and it may precede systemic involvement by either myelodysplastic syndrome or acute leukaemia.     

Acute generalized exanthematous pustulosis-like, folliculitic drug reaction pattern caused by celecoxib

An extensive range of diseases or reactions can cause pustular eruptions of the skin. Drug-provoked cutaneous eruptions includes acute generalized exanthematous pustulosis (AGEP) and acneiform eruption. We report a 50-year-old man who developed fever and a sudden eruption of widespread pustules 12 days after ingestion of celecoxib prescribed for a prolapsed intervertebral disc. AGEP was diagnosed based on the typical history, characteristic features, and laboratory findings. However, histopathological findings were consistent with folliculitic drug reaction pattern without features of AGEP. We present, the first known reported case of folliculitic drug reaction pattern caused by celecoxib.     

Generalized pustular psoriasis with hypoparathyroidism.

A 36-year-old Japanese woman with pustular psoriasis associated with hypoparathyroidisum was reported. The patient showed hypocalcemia and was treated with calcium supplements and calcitriol. When the serum calcium level became normal, the pustules disappeared and erythroderma completely resolved. Histopathological features consisted of the formation of intraepidermal pustules including spongiform pustules underneath the stratum corneum, and acantholysis was observed in the epidermis. It was suggested that generalized pustular psoriasis may have been induced by hypocalcemia due to hypoparathyroidism in this case, and that acantholysis may be caused by hypocalcemia, since intercellular junctional components such as cadherins are highly dependent on calcium in the epidermis.     

Pustular herpes gestationis

Pustular eruptions during pregnancy and the puerperium are rare. A case of herpes gestationis (HG) in which the lesions were predominantly pustules and in which a vesicular or bullous component was not noted is reported. The differential diagnosis of pustular eruptions associated with pregnancy is discussed.     

Eosinophilic pustular folliculitis starting initially only with palmoplantar pustular lesions. Report of a case and review of the literature.

We report a 23-year-old Japanese male with eosinophilic pustular folliculitis (EPF) that had started with palmoplantar rash. Only when follicular pustules appeared on the bilateral cheek 31 months later, we revised our initial diagnosis of pustulosis palmaris et plantaris (PPP) to EPF, and all the skin eruptions cleared mostly with indomethacin. A review of the Japanese literature for the past 20 years disclosed that in 207 cases of EPF so far reported, palmoplantar pustular lesion was noted in 38 (18%). Among them, in 16 cases (8%) the skin lesions started first from the palmoplantar region with the average period of 26 months until the appearance of other eruptions of EPF. None of them was diagnosed as EPF when skin lesions were localized only to the palmoplantar region. When we find pustules on the palmoplantar region, we should suspect the possibility of early lesions of EPF as well as PPP. Histopathologic demonstration of multilocular pustules located in the upper epidermis containing numerous eosinophils in the palmoplantar pustular lesions, together with the dramatic therapeutic response to indomethacin greatly favor the diagnosis of EPF.     

Case of acrodermatitis continua of Hallopeau following psoriasis with atypical clinical presentation

We present a 63‐year‐old Japanese woman who had clinically unique symmetrical skin rashes on her lower face, inframammary area, back and extremities, with some pustules on the cheeks. Skin biopsy specimens showed typical findings of psoriasis, and Psoriasis Area and Severity Index score was 5.9. After the skin lesions were treated successfully with vitamin D3 ointment, pustules developed on the tips of the fingers and toes, with paronychial and subungual involvement. The pathology of the nail matrix was consistent with pustular psoriasis, and the patient was diagnosed with acrodermatitis continua of Hallopeau (ACH) following psoriasis with an unusual clinical presentation. ACH was well controlled with a low dose of cyclosporin. Our patient is a rare case chronologically affected by two diseases in the same category. We confirmed that ACH is a variant of pustular psoriasis, and believe that the patient could provide another clue to determining the entity of ACH.     

Subcorneal pustules in erythema multiforme

A man aged 24, suffering from Stevens Johnson syndrome precipitated by an upper respiratory infection, developed a skin eruption which consisted of sterile pustules. Histological examination showed subcorneal pustules containing polymorphonuciear leukocytes and no abnormality of the basal part of the epidermis, an appearance indistinguishable from subcorncal pustular dermatosis. The eruption cleared rapidly and did not recur. It is emphasized that the histological appearance of a subcorneal pustule does not necessarily indicate a diagnosis of subcorneat pustular dermatosis (Sneddon & Wilkinson, 1956).     

Acute generalized exanthematous pustulosis (AGEP)--a clinical reaction pattern

BACKGROUND: A wide range of diseases or reactions can cause pustular eruptions of the skin. In this spectrum there seems to be a subgroup with characteristic clinical features and a typical course which is mostly caused by drugs for which the term acute generalized exanthematous pustulosis (AGEP) has been established. OBJECTIVE: To describe the clinical features of AGEP. METHODS: The authors' experience from a multinational epidemiological study on severe cutaneous adverse reactions and a comprehensive review of the literature were used to provide an overview of the disease and it's possible causes. An algorithm for validating cases which was established for this study is also presented. RESULTS: AGEP typically presents with at least dozens of non follicular sterile pustules occurring on a diffuse, edematous erythema predominantly in the folds and/or on the face. Fever and elevated blood neutrophils are common. Histopathology typically shows spongiform subcorneal and/or intraepidermal pustules, a marked edema of the papillary dermis, and eventually vasculitis, eosinophils and/or focal necrosis of keratinocytes. Onset is acute, most often following drug intake, but viral infections can also trigger the disease. Pustules resolve spontaneously in less than 15 days. CONCLUSION: The diagnosis AGEP should be considered in cases of acute pustular rashes and detection of the causative drug should be strived for. Knowledge of the clinical features and usual course of this disease can often prevent unnecessary therapeutical measures.     

头皮糜烂性脓疱性皮病一例

患者,女,50岁.头皮红斑、脓疱伴疼痛6个月.皮肤科查体:头皮弥漫性分布紫红色浸润性斑片,其上见脓疱,局部见斑片状脱发区.实验室检查:取脓疱疱液多次行细菌及真菌培养均阴性.组织病理:表皮角化过度伴角化不全;真皮浅中层弥漫性淋巴细胞、浆细胞、中性粒细胞浸润.抗生素治疗效果不佳,口服糖皮质激素及外用他克莫司治疗后有效.诊断...     

Diagnosis and Treatment of Pustular Disorders in the Neonate

Abstract: The diagnosis of a pustular dermatosis occurring during the first months of life is usually based on clinical findings. However, some cases may require simple investigations including microscopic examination of pustular content, cultures, and skin biopsies. The main benign transient neonatal types of pustulosis include erythema toxicum neonatorum, infantile acropustulosis, transient neonatal pustular melanosis, and neonatal acne. The most common causes of infectious pustular skin lesions include bacterial infections, which may be initially localized (Staphylococcus aureus) or septicemic (with Listeria monocytogenes as the leading causitive agent); viral infections (herpes simplex, varicella-zoster, and cytomegalovlrus infections); fungal infections (candidiasis); or parasitic disorders (scabies). The main objective of this article is to propose a systematic approach to pustular eruptions in the neonate. The need for investigating every neonate with pustules for an infectious disease is emphasized. The Tzanck smear, the Gram's stain, and a potassium hydroxide preparation are the most important quick diagnostic tests. The Tzanck smear is a very easy, rapid, and sensitive test for detection of a herpetic infection (multinucleated giant cells) as well as noninfectious pustular eruptions (eosinophils, neutrophils). Therefore the Tzanck smear should be the first test performed. Moreover, a Gram's stain and potassium hydroxide preparation should be performed in cases of neonatal pustular disorders to detect bacterial and fungal infections. The goal of this diagnostic approach is to spare a healthy neonate with a benign transient condition an invasive evaluation for sepsis, potentially harmful antibiotic therapy, and prolonged hospitalization, with its own inherent morbidity.     

Skin reactions in a subset of patients with stage IV melanoma treated with anti-cytotoxic T-lymphocyte antigen 4 monoclonal antibody as a single agent

OBJECTIVE: To describe the clinical and histologic manifestations of skin reactions incidentally noted in patients with stage IV melanoma who were treated with up to 9 mg/kg of a humanized monoclonal antibody reactive against human cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) as a single agent every 3 weeks. SETTING: Single-institution prospective study. DESIGN: Patients treated with anti-CTLA-4 as a sole agent were prospectively referred for clinicopathologic characterization of skin reactions occurring during treatment. MAIN OUTCOME MEASURES: Specific clinicopathologic features were determined by means of a detailed history, a physical examination, conventional histologic analysis, antibody staining, and complete blood cell counts. RESULTS: Nine (14%) of 63 consecutive patients treated with anti-CTLA-4 as a sole agent developed skin eruptions that were attributed to anti-CTLA-4 in 8 of them. Skin lesions consisted primarily of discrete, pruritic, erythematous, minimally scaly papules that typically coalesced into thin plaques on the trunk and extensor surfaces of the extremities. Extensive alopecia was also noted in 1 patient. Histologically, a superficial, perivascular CD4+-predominant T-cell infiltrate with eosinophils in the dermis, rare dyskeratotic cells, and mild epidermal spongiosis were present. An increase (compared with pretreatment values) in the peripheral blood eosinophil frequency was observed in patients at the time of skin eruptions (P = .006). CONCLUSIONS: Specific features of the skin eruption dermatitis with increased tissue and peripheral blood eosinophil levels in a subset of treated patients. Specific features of skin eruption associated with anti-CTLA-4 resemble those described for maculopapular reactions to medications.     

Hyperimmunoglobin E syndrome: a sign of TH1/TH2 imbalance?

We report on a patient with hyperimmunoglobulin E syndrome, who developed pruritic vesiculopapules from the age of six months and also had recurrent episodes of skin abscesses and oral thrush. Serum IgE was extremely elevated at 59,514 IU/ml and specific IgE antibody to Staphylococcus aureus was positive. Histological examination from a vesiculopapule on the face revealed that eosinophil-rich infiltration involved hair follicles, similar to eosinophilic pustular folliculitis. We also examined cytokine profiles of circulating CD4+ T cells by intracellular cytokine staining and flow cytometry. The ratio of cells positive for interferon-gamma was significantly reduced compared with a control. Several reports have shown decreased interferon-gamma production by peripheral blood mononuclear cells of patients with hyperimmunoglobulin E syndrome. We think that this cytokine profile and the histological findings of our patient support the hypothesis that TH1/TH2 imbalance is involved in hyperimmunoglobulin E syndrome.