Granulocytic Spongiotic Papulovesiculosis (Neutrophilic Spongiosis): A Rare Entity.

Neutrophilic spongiosis also known as granulocytic spongiotic papulovesiculosis (GSPV) is an uncommon disorder of uncertain classification. We report the case of a 45-year-old woman suffering from recurrent episodes of itchy, grouped papulovesicles over her body, histologically showing granulocytic spongiosis. The eruptions showed complete response to dapsone.

What was known?

Granulocytic spongiotic papulovesiculosis is a rare entity considered under the spectrum of neutrophilic dermatoses. It is characterized by intermittent outbreaks of myriad, semiconfluent, small papulovesicles, and vesicopustules, with marked neutrophilic spongiosis on histopathology.

Introduction

Neutrophilic spongiosis was reported for the first time in 1984 by Dr. Sayami and Dr. Tagami who proposed the term “Granulocytic spongiotic papulovesiculosis (GSPV)” for it.[1] It is a disorder of uncertain classification and the etiology has never been fully explained. Literature has only 2 cases on record so far.[12] The reported cases showed recurrent outbreaks of small, vesicopustules, predominantly on face, neck, or upper trunk with unique histopathological features of epidermal granulocytic spongiosis, neutrophilic exocytosis without any evidence of vasculitis. This condition is usually steroid resistant and dapsone responsive. Relapses are common after stopping the treatment.

Case Report

A 45-year-old female presented with rapidly progressing grouped red raised, itchy, nontender lesions over lower legs, hands, face, abdomen, and lower back with moderate fever 100-102 degree F for the past 2 weeks. History of similar episodes (for the past 4 years) more in summers was obtained. Successive crops appeared, persisted for 3–4 weeks, and resolved, leaving behind postinflammatory hyperpigmentation. She also had symmetrical, nonmigratory joint pains involving the interphalangeal, wrists, knee, ankle, and metarsophalangeal joints without any associated swelling and redness for the past 4 years. There was no history of recurrent oral/genital ulcers, raynaud's phenomenon, photosensitivity, muscle weakness, gastrointestinal complaints, prior drug intake, or history of any topical irritant or allergen application. Family history was noncontributory. She was receiving tablet amlodipine 5 mg for the last 3 months.

General physical examination was normal. On cutaneous examination, multiple grouped erythematous to violaceous papulovesicles and vesicopustules of size 0.3 cm × 0.3 cm–0.5 cm × 0.5 cm were present over abdomen, lower trunk, arms, hands, feet, and face [Figures 1 and 2]. Few interspersed erosiocrusted plaques and koebnerization were evident. Few erythematous to violaceous plaques of size 0.7 cm × 0.7 cm–1 cm × 1 cm were present over the forehead, surface showed fine white semiadherent scaling [Figure 3]. Examination of scalp, oral mucosa, palms, soles, and nails was within normal limits.

Figure 1

Multiple grouped erythematous to violaceous papulovesicles on shoulder

Figure 2

Multiple grouped erythematous to violaceous papulovesicles and crusting

Figure 3

Erythematous to violaceous plaques over the forehead

Based on these findings, possibility of contact dermatitis, lupus erythematosus, and neutrophilic dermatosis (sweet's syndrome) was kept.

Routine hematological and biochemical investigations were normal. Erythrocyte sedimentation rate was raised (34 mm). Antinuclear antibody, rheumatoid factor, perinuclear antineutrophil cytoplasmic antibodies (ANCA), cytoplastic ANCA, antistreptolysin O, C-reactive protein, hepatitis B and C antibody were negative. Electrocardiograph did not reveal any abnormal change. Radiographs of bilateral knee joints revealed degenerative changes while that of chest, bilateral hands, feet, and wrist joints were within normal limits.

Histopathological examination of a papule showed mild hyperkeratoses, focal spongiosis, and neutrophilic exocytosis of the epidermis [Figure 4]. It also showed intraepidermal pustule containing neutrophils and few eosinophils [Figure 5]. Dermis showed mild pigment incontinence and perivascular inflammatory infiltrate of neutrophils and few eosinophils till mid-dermis. Dermal capillaries had plump endothelial cell lining but no fibrinoid necrosis. Direct immunofluorescence (DIF) showed no deposition of immunoreactants.

Figure 4

Focal spongiosis and neutrophilic exocytosis of the epidermis (H and E, ×10)

Figure 5

Intraepidermal pustule containing neutrophils and few eosinophils (H and E, ×40)

The patient was initially started on oral prednisolone, with only partial improvement and continuous development of new lesions. She was then started on oral dapsone 100 mg daily. The lesions resolved in 4–5 days leaving behind pigmentation. Dapsone was gradually tapered and stopped in 8 weeks. The patient has not developed any new lesion in 4 months of follow-up.

Discussion

GSPV is characterized by intermittent outbreaks of myriad, semiconfluent, small papulovesicles, and vesicopustules, predominantly on the face, neck, or upper trunk but sometimes over other sites such as axillae.[3] Only 2 cases have so far been described in literature. The features of these cases are shown in Table 1. Palms, soles, scalp, and nails are usually spared. Predominant flexural and severe mucosal involvement of the entire oral, pharyngeal, and vaginal mucous membranes were reported in one patient.[2] Our patient presented with recurrent episodes of rapidly progressing pruritic grouped papulovesicles over face, trunk, and upper limbs. She had no mucosal involvement.

Table 1

Features of cases reported in literature

The histopathological findings of GSPV are unique showing epidermal granulocytic spongiosis, neutrophilic exocytosis with vesicles containing neutrophils and eosinophils, and not fulfilling the features of vasculitis.[1] These features are similar to the findings in our patient.

The histological features of neutrophilic spongiosis can be seen in several conditions as enumerated in Table 2. Sweet's syndrome has certain diagnostic criteria which are not fulfilled by our patient. The lesions in our patient were nontender unlike in sweet's syndrome. The histology of sweet's syndrome shows dense, predominantly neutrophilic, infiltrate located in the superficial dermis in a band-like pattern, and prominent papillary dermal edema which may occasionally lead to subepidermal vesiculation. Lymphocytes, eosinophils, and “histiocytes” may be present. Neutrophil karyorrhexis (fragmented neutrophil nuclei; nuclear dust) is a common finding. Furthermore, sweet's syndrome responds dramatically to steroids, which was not seen in our patient. Thus, the clinical and laboratory data along with dramatic response to dapsone in our patient preclude the possibility of sweet's syndrome and other disorders as mentioned in Table 2. Subcorneal pustular dermatoses present with chronic, recurrent vesiculopustular eruptions. However, papules or papulovesicles are rarely seen, unlike in GSPV. The lesions coalesce into annular, circinate or serpinginous patterns, preferring the trunk and intertriginous areas, including the axillae, groin, and submammary regions. Histopathologically, the hallmark of subcorneal pustular dermatosis is a strictly subcorneal pustule filled with polymorphonuclear leukocytes. The underlying epidermis is generally spared and spongiosis is usually absent which help in differentiating it from GSPV. Hence, the diagnosis of GSPV was made.

Table 2

Differential diagnosis of neutrophilic spongiotic vesiculopustular dermatoses

DIF in GSPV is usually negative, but a positive DIF with IgA deposition at the dermoepidermal junction was noted in a single patient.[2] Our patient had a negative DIF.

Our patient had certain distinct features such as association with multiple joint pains (attributed to systemic inflammation), fever, itching, and increased frequency of lesions in summers. Another interesting feature in our patient was koebnerization, which has not been reported so far in this disease.

Treatment with rifampicin, gentamicin, erythromycin, antihistamines, corticosteroids, azathioprine, methotrexate, and colchicine is usually ineffective. GSPV responds dramatically to dapsone in 48–72 h. Clofazimine was tried in a patient intolerant to dapsone, which showed therapeutic response similar to that with dapsone.[2] Relapses are quite common after stopping the drugs. Our patient showed poor response to steroids, and hence, dapsone was started with response seen in 3–4 days.

We report this case for its rarity. Since this condition has several close differentials, it can be easily missed out and misinterpreted. Hence, GSPV can be suggested as a diagnosis although uncommon, especially where neutrophilic spongiosis is encountered as the predominant feature on histopathology.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

What is new?

GSPV is a rare entity with several close differentials. Dermatologists should consider this possibility in any patient presenting with recurrent episodes of papulovesicles showing neutrophilic spongiosis on histopathology. It can show koebnerization and rapid response to dapsone.