Kimura disease

H.BasavanaGowdappa, BhanuKumar, M.G.Mahesh,Syed,Nikhil,Cijo,Snigdha

A 23 year old male patient presented with complaints of swelling of both lower limbs and abdominal distension of one week duration. He was not an alcoholic. There was no history of neuro-psychiatric symptoms or any other significant complaints. Patient had history of jaundice at the age of two.

Examination revealed bilateral pitting pedal edema. There was no icterus. Incidentally, he was found to have bilateral cervical, axillary, inguinal lymph nodes of approximately 1-1.5 cm each, which were non-tender. There were no Kayser-Fleischer rings on slit lamp examination. Patient had firm, nontender hepatomegaly, moderate splenomegaly and moderate ascites. Other systems were clinically normal.

With this constellation of symptoms and signs, a differential diagnosis of a haematological malignancy (leukemia or lymphoma) or disseminated tuberculosis was considered.

Investigations - Hb 13.3 g/dl, Total WBC Count 19,400 cells/cumm, Differential of N78L16E04, ESR 25 mm/hr, Platelet count 2.11 lakhs /cumm. Urine had NO albumin or sugar and 1-2 pus cells and 1-2 epithelial cells.
RBS 104 mg/dl, Blood urea 24 mg/dl, Serum creatinine 1.0 mg/dl. Liver function tests revealed Total bilirubin 1.0 mg/dl , Direct bilirubin 0.70 mg/dl, Total protein 6.0 g/dl, Serum Albumin 3.3 g/dl , A:G ratio 1.1, AST 45, ALT 33, Alkaline phosphatase 419. Prothrombin time INR was 1.25, APTT 1.29. Bleeding time 3’00” and Clotting time of 4’00”.

Ascitic fluid was analysis revealed a cell count of 50 cells/cumm, Cell type predominantly lymphocytes, few neutrophils and occasional mesothelial cells. Gram’s stain showed few lymphocytes but no organisms. AFB stain was negative for acid-fast bacilli. Ascitic fluid Glucose was 126 mg/dl, protein 0.8 g/dl. SA-AG (Serum Albumin-Ascitic albumin) gradient was 2.5, suggestive of transudative ascites.
Viral markers (HBsAg, Anti HCV) were negative. HIV was negative. Anti Nuclear antibody test was negative. Serum Ceruloplasmin 23.4 mg/dl α1-Antitrypsin 2.56g/l. Ultrasound abdomen showed slightly enlarged liver with heterogenous echotexture, multiple ill-defined hypoechoic mass lesions in both lobes, mild splenomegaly, Moderate ascites. Features suggestive of Chronic liver disease to rule out underlying malignancy.Upper GI endoscopy showed Grade 1 Esophageal varices and Portal Hypertension. CT scan abdomen showed Nodular surface of liver, mild to moderate ascites, Multiple enlarged mesenteric lymph nodes, mildly enlarged spleen. Other abdominal organs were normal. CT features were suspicious of cirrhosis of liver with ascites and with mesenteric lymphadenopathy.

FNAC of cervical lymph node showed lymphoid series of cells in various stages of maturation; many histiocytes, occasional giant cells and plenty of eosinophils. Liver biopsy showed ballooning degeneration of hepatocytes with loss of normal architecture and formation of pseudolobules. Fibrous septae with foci of cholestasis was also seen. Reticulin staining showed increase in fibroblasts. All these features were suggestive of Cirrhosis of liver.

In view of inconclusive FNAC report, Axillary lymph node excision biopsy was undertaken. Histopathological study of which revealed marked hyperplasia of follicles, large number of eosinophils, neutrophils and plasma cells. Many hyalinised blood vessels were seen- features suggestive of Kimura disease.

Hence a final diagnosis of Cirrhosis liver probably cryptogenic post infective etiology with Kimura disease was arrived at. The patient was put on a low-salt fluid restricted diet along with diuretics with which he symptomatically improved. Kimura disease warranted no treatment in him at this stage.

Kimura disease

Kimura disease is a rare benign chronic inflammatory disorder. It was first described in 1937 (Kim et al) from China and later popularized in 1948 by Kimura and his associates who noted a change in the surrounding blood vessels and referred to it as "unusual granulation combined with hyperplastic changes in lymphoid tissue."

Kimura Disease is predominantly seen in males of Asian descent. The cause of Kimura disease remains unknown. Reasons like an allergic reaction or an alteration of immune regulation are suspected. Other theories like persistent antigenic stimulation following arthropod bites and parasitic or candidal infection have also been proposed. To date, none of these theories have been substantiated.

It typically presents as non-tender subcutaneous swelling in head and neck region, predominantly in preauricular and submandibular area. It is associated with lymphadenopathy both local and distal, marked peripheral eosinophilia and an elevated IgE level. The disease is manifested by an abnormal proliferation of lymphoid follicles and vascular endothelium.

Renal involvement is the only systemic manifestation which may affect up to 60% of patients as membranous glomerulonerphritis, minimal change glomerulonephritis, diffuse proliferative glomerulonephritis, mesangial proliferative glomerulonephritis and also nephrotic syndrome (12% of cases).

Differential diagnosis include

.

· Eosinophilic granuloma

· Mikulicz's disease

· Acute lymphocytic leukaemia

· Hodgkins disease

· Angioimmunoblastic lymphadenopathy

It can easily be mistaken for a malignant disorder. FNAC is misleading and diagnosis is established only on histopathological examination.

Treatment: Observation is acceptable if the lesions are neither symptomatic nor disfiguring. Intralesional or oral steroids can shrink the nodules but seldom result in cure. Cetirizine is an effective agent in treating the symptoms of Kimura's disease. Radiotherapy has been used to treat recurrent or persistent lesions. However, considering the benign nature of this disease, radiation should be considered only in cases of recurrent, disfiguring lesions. Surgery has been considered the mainstay of therapy. However, recurrence after surgery is common.

Kimuras Disease should be considered in differential diagnosis in patients who present with primary lymphadenopathy with Eosinophilia and investigated accordingly as the disease has an indolent course and good prognosis.

Acknowledgements

We sincerely thank Dr.Manjunath, Professor & Head Pathology, Dr.Sunila, Professor of Pathology for their help extended during work-up of this case.

References

1. Kim HT, Szeto C. Eosinophilic hyperplastic lymphogranuloma, comparison with Mikulicz’s disease.Chin Med J 1937; 23:699-700.

2. Kimura T, Voshimura S, Ishikawa E. On the unusual granulation combined with hyperplastic changes of lymphatic tissues. Trans Soc Pathol Jpn 1948; 37:170-80.

3. Messina T. M. D., Armstrong W. B., Pena F. et al (1998) : Kimura's disease two case reports and a literature review. Annals of Otology, Rhinology and Laryngology 107 (12) : 1066-71.

4. Kung I. T. M., Gibson J. B., Bannatyne P. M. (1984) : Kimura's disease : A clinico-Pathological study of 21 cases and its distinction from angiolymphoid hyperplasia and eosinophilia.Pathology 16 : 39-44.

5. Googe PB, Harris NL, Mihm MC Jr. Kimura’s disease and angiolymphoid hyperplasia with eosinophilia: two distinct histopathological entities. J Cut Pathol 1987; 12:263-71.

6. Chusid M. J., Rock A. L., Sty J. R. et al (1997) : Kinmura's disease : an unusual cause of cervical tumor. Archives of disease in childhood 77 (2) : 153-4.

A case of SLE with quadriparesis and skin manifestations

Dr. K.A. Sudharshana Murthy, Dr. Kiran.H.S., Dr. Thippeswamy, Dr. Vijay Cheluvaraj, Dr. Aparna.A.N., Dr. Pramod Chebbi, Dr. Sriram Chandrudu

A 35 year old lady presented to the ER with history of joint pain of 6 months, intermittent fever of 6 months, quadriparesis of 15 days, and hyperpigmented skin lesions over exposed areas since 5 days. There was no history of similar episodes in the past. Patient was not a diabetic or a hypertensive.

On examination patient had facial puffiness, hyperpigmented lesions over the legs and forearms. Her radial artery pulsations were felt and was 84/min whereas her lower limb pulsations were absent bilaterally upto the popliteal artery. Her blood pressure in both the upper limbs was 104/80 mm of Hg. She had quadriparesis and generalized areflexia. There were no sensory system or cranial nerve involvement. Higher mental functions were normal.

Figure 1: Hyperpigmented ecchymotic patches over the legs with gangrenous changes of the toes

Patient was further evaluated with skin biopsy and blood investigations which revealed the following: Hb- 8.6g/dl, TLC - 10,800/cu mm, DLC-N78 L18 E4, ESR- 30mm, Platelet count- 2.05 lakh/cu mm,Urea- 128 mg/dl, Creatinine- 1.9 mg/dl, Na- 136 mmol/l, K- 5 mmol/l

Rheumatoid factor: negative, ANA: positive,ds- DNA: positive, HIV: non-reactive.Arterial and venous Doppler studies of both the lower limbs were normal. Renal artery doppler- normal. Nerve conduction study: not excitable b/l radial nerve at wrist, b/l ulnar nerve at wrist, b/l peroneal nerve.

Figure 2: Deposition of keratinocytes along the blood vessels and basement membrane

Figure 3: DIF studies show discontinuous granular deposits of IgG, IgA and IgM along basement membrane zone. Deposition of IgG and IgA are also seen around basement membrane of sweat glands and blood vessels -features suggestive of cutaneous small vessel vasculitis.

Discussion

Vasculitis is a spectrum of clinicopathological disorders defined by inflammation of the blood vessels, including arteries and veins of varying caliber, which result in a variety of clinical neurological manifestations related to ischemic injury of the central nervous system (CNS) and peripheral nervous system (PNS). Peripheral neuropathy is a well-recognized consequence of systemic vasculitis due to peripheral nerve infarction with Wallerian degeneration. Rarely, neuropathy is the sole manifestation of vasculitis, referred to as nonsystemic vasculitic neuropathy (NSVN). These conditions are defined pathologically by tissue biopsy demonstrating disruption or destruction of the vessel wall with inflammatory cell infiltrates.

The diagnosis of vasculitic neuropathy is straightforward in patients with an established diagnosis of systemic vasculitis and classic features of mononeuritis multiplex. Most patients have clinical features of a subacute, progressive, generalized but asymmetric, painful, sensorimotor polyneuropathy. Classically, patients have painful sensory loss and weakness in the distribution of multiple peripheral nerves, referred to as mononeuritis multiplex. Pain also may be described as burning and often occurs in the distribution of affected nerve territories (eg, ulnar or peroneal sensory nerve distributions).

Symptoms develop in a stepwise progressive pattern evolving over weeks to months; occasionally, patients worsen rapidly over days and develop a painful quadriparesis. Others, particularly elderly patients, have an indolent course with progression over many months or a year or more. The latter pattern is especially common in patients with nonsystemic vasculitic neuropathy (NSVN). Similarly, vasculitic neuropathy is virtually never a pure motor condition; patients have symptoms of numbness or paresthesias and findings of sensory impairment in clinically affected regions.

. Laboratory tests often indicate features of systemic inflammation, such as an elevated sedimentation rate or positive anti-neutrophil cytoplasmic antibody, and electrodiagnostic evaluation shows multiple mononeuropathies or a confluent, asymmetric axonal neuropathy.

Because partial ischemic lesions may occur along the course of several nerves simultaneously, it may not be appreciated that the majority of patients have a confluence of multiple mononeuropathies, producing a generalized but multifocal and asymmetric polyneuropathy, or a lumbosacral plexus neuropathy when limited to the legs. A few patients have a distal, symmetric, pure sensory or sensorimotor polyneuropathy.

Table 1: Primary and secondary Systemic Vasculitis Associated With Neuropathy: Clinical and Laboratory Features.

TREATMENT

Standard therapy is combined treatment with prednisone, 1.0 mg/kg/d, and either cyclophosphamide, 1–2mg/kg/d orally, or intravenous pulse cyclophosphamide at a dosage of 1g/m.

Azathioprine is used as adjunctive therapy for vasculitic neuropathy and is an effective steroid sparing agent and safer alternative to cyclophosphamide. The benefit may not be apparent for at least 6 months after initiating treatment. It is administered as a single daily dosage of 2 to 3mg/kg/d administered orally, starting at 50 mg/d for the first several days to a week, followed by slow-dosage escalation of 50 mg every few days to the desired dose.

Our patient was treated with steroids and cyclophosphamide. Patient’s power has improved and her progression of skin lesions has been disrupted due to medications.

CONCLUSION

Systemic lupus erythematosus is a common entity. A rare possibility of quadriparesis with skin manifestations should direct us towards diagnosing vasculitis and prompt treatment should be initiated to prevent worsening of the disease.